Table S1 Mutants of neuronal signaling genes tested
Gene
aap-1
Allele and
Strain ID
aap-1(m889)
DR2278
ace-3
ace-3(dc2)
PR1300
acr-10
acr-10
(ok3118) VC2661
acr-11
acr-11
(ok1345) RB1263
acr-12(ok367)
VC188
acr-12
acr-14
acr-15
acr-16
acr-14
(ok1155) RB1132
acr-15(ok1214)
RB1172
acr-16(ok798)
RB918
acr-23
acr-23(ok2804)
RB2119
acr-3
acr-3(ok2049)
RB1659
acr-7
acr-7(tm863)
FX863
acr-9
acr-9(ok933)
VC649
WormBase Gene Description
aap-1 encodes the C. elegans ortholog of the phosphoinositide 3-kinase (PI3K) p50/p55
adaptor/regulatory subunit; AAP-1 negatively regulates lifespan and dauer development, and likely
functions as the sole adaptor subunit for the AGE-1/p110 PI3K catalytic subunit to which it binds in
vitro; although AAP-1 potentiates insulin-like signaling, it is not absolutely required for insulin-like
signaling under most conditions.
ace-3 encodes one of four C. elegans acetylcholinesterases (AChE); ACE-3 represents ~5% of the
total AChE activity in C. elegans and in vitro, hydrolyzes acetylthio-, butyrylthio-, and
propionylthiocholine substrates with equal efficiency; although loss-of-function mutations in ace-3
result in no obvious defects, animals doubly mutant with ace-1 or ace-2 have slight defects in
backward locomotion and animals triply mutant for ace-1, -2, and -3 arrest as unhatched, yet fully
developed, embryos; ace-3 is the downstream gene in an operon with a fourth AChE-encoding gene,
ace-4, and transcriptional reporter fusions with ace-4 upstream sequences direct expression in
pharyngeal muscles pm3, 4, 5, and 7, the two CAN (canal associated neuron) cells, midbody dorsal
body wall muscles in larvae, and several neurons in the head and anal ganglion
acr-10 encodes an alpha-7-like homomer-forming subunit of the nicotinic acetylcholine receptor
(nAChR) superfamily which encode ligand-gated ion channels that regulate fast action of
acetylcholine at neuromuscular junctions and in the nervous system; ACR-10 is a member of the
ACR-16-like group of nAChR subunits.
A homolog of an alpha type nicotinic acetylcholine receptor subunit involved in the mediation of
fast synaptic transmission at neuromuscular junctions.
acr-12 encodes a nicotinic acetylcholine receptor (nAChR) alpha subunit that is a member of the
ACR-8-like group of C. elegans nAChR subunits; as an nAChR subunit, ACR-12 is predicted to
mediate fast excitatory neurotransmission, however loss of acr-12 activity via mutation or RNAi
results in no obvious defects; ACR-12 copurifies with UNC-29 and LEV-1, suggesting that ACR-12
can form receptors with these two non-alpha AChR subunits; an ACR-12::GFP fusion protein is
expressed exclusively in ventral cord motor neurons, including the D neurons; in vivo, ACR-12
colocalizes with some, but not all, UNC-38-containing postsynaptic receptor clusters, suggesting
that ACR-12 contributes to only a subset of these receptor clusters.
acr-14 encodes a protein that contains neurotransmitter-gated ion-channel ligand-binding and
transmembrane domains.
A homolog of an alpha type nicotinic acetylcholine receptor subunit involved in the mediation of
fast synaptic transmission at neuromuscular junctions.
acr-16 encodes an alpha-7-like homomer-forming subunit of the nicotinic acetylcholine receptor
(nAChR) superfamily orthologous to human nicotinic cholinergic receptor alpha 7 (CHRNA7;
OMIM:118511; possibly associated with schizophrenia and juvenile myoclonic epilepsy); ACR-16
functions as a ligand-gated ion channel that is required for the major fast cholinergic excitatory
current at C. elegans neuromuscular junctions; an ACR-16::GFP reporter fusion expressed in muscle
cells localizes to the tips of muscle arms, specific regions of the muscle cell membrane that form
synapses with neuronal processes; acr-16::gfp promoter fusions also reveal expression in a subset of
neurons; when expressed in Xenopus ooctyes, ACR-16 is active as a homomeric receptor and
responds robustly to acetylcholine.
acr-23 encodes an alpha 7-like homomer-forming subunit of the nicotinic acetylcholine receptor
(nAChR) superfamily which encode ligand-gated ion channels that regulate fast action of
acetylcholine at neuromuscular junctions and in the nervous system; ACR-23 is a member of the
DEG-3-like group of nAChR subunits which appears to be unique to nematodes.
acr-3 encodes a non-alpha subunit of the nicotinic acetylcholine receptor (nAChR) superfamily;
ACR-3 functions as a ligand-gated ion channel that likely mediates fast actions of acetylcholine at
neuromuscular junctions and in the nervous system; when coexpressed with UNC-38, an nAChR
alpha subunit, the resulting hetero-oligomer can form levamisole-gated channels; ACR-3 is a
member of the UNC-29-like group of nAChR subunits.
acr-7 encodes an alpha-7-like homomer-forming subunit of the nicotinic acetylcholine receptor
(nAChR) superfamily which encode ligand-gated ion channels that regulate fast action of
acetylcholine at neuromuscular junctions and in the nervous system; ACR-7 is expressed pharyngeal
muscle and in tail neurons distal to the anus, and is a member of the ACR-16-like group of nAChR
subunits.
acr-9 encodes a predicted member of the alpha subunit family of nicotinic acetylcholine receptors.
acy-1
acy-1(md1756)
KG522
aex-3
aex-3(sa5)
JT5
aex-6
aex-6(sa24)
JT24
age-1
age-1(hx546)
TJ1052
ags-3
ags-3(ok1169)
RB1145
ahr-1
ahr-1(ju145)
CZ2485
alr-1
alr-1(oy42)
PY1598
ant-1.4
ant-1.4(gk300)
VC652
acy-1 encodes an adenylyl cyclase that is most closely related to the divergent mouse isoform type
IX; acy-1 is required for viability, muscle contraction, locomotion, molting, and regulation of sleeplike behavior (lethargus) during larval development; acy-1 acts genetically downstream of gsa-1 and
is expressed in excitable cells.
aex-3 encodes a guanine nucleotide exchange factor for the rab-3 GTPase that is orthologous to
human MAP kinase activating protein containing death domain (MADD, OMIM:603584); AEX-3 is
required for intracellular vesicle trafficking as well as synaptic vesicle release and interacts with
CAB-1 and RAB-3 to regulate separate pathways for neural activities such as defecation and male
mating, respectively; AEX-3 is also required for egg laying and locomotion; AEX-3 is expressed in
nearly all neurons.
aex-6 encodes a Rab small GTPase; aex-6 was identified in screens for defecation defective mutants
and high-temperature-induced dauer formation mutants; aex-6 appears to act in the insulin branch of
the dauer pathway; aex-6 is genetically required for two different steps of normal defecation in the
hermaphrodite digestive tract; since its mutant phenotype resembles that induced by ablation of the
interneuron AVL and the motor neuron DVB, aex-6 is likely to be required for the function or
activation of these neurons rather than for any of their specific neurotransmitter systems; aex-6::gfp
reporter fusions are expressed in neurons and in the intestine; in the nervous system, AEX-6
localizes to synapse-rich regions and partially colocalizes with synaptic vesicle-associated RAB-3.
age-1 encodes the C. elegans ortholog of the phosphoinositide 3-kinase (PI3K) p110 catalytic
subunit; AGE-1, supplied maternally and embryonically, is a central component of the C. elegans
insulin-like signaling pathway, lying downstream of the DAF-2/insulin receptor and upstream of
both the PDK-1 and AKT-1/AKT-2 kinases and the DAF-16 forkhead type transcription factor,
whose negative regulation is the key output of the insulin signaling pathway; in accordance with its
role in insulin signaling, AGE-1 activity is required for regulation of metabolism, life span, dauer
formation, stress resistance, salt chemotaxis learning, fertility, and embryonic development;
although the age-1 expression pattern has not yet been reported, ectopic expression studies indicate
that pan-neuronal age-1 expression is sufficient to rescue life-span defects, while neuronal,
intestinal, or muscle expression can partially rescue dauer formation, and neuronal or muscle
expression can rescue metabolic defects.
ags-3 encodes a protein containing N-terminal TRP domains and C-terminal GPR domains that is a
member of the Activator of G Protein Signaling 3 (AGS3) family of proteins that includes
mammalian AGS3 and LPN and Drosophila RAPSYNOID; in C. elegans, AGS-3 is involved in
polarity and spindle orientation during early embryogenesis; in addition, AGS-3, along with the
RIC-8 guanine nucleotide exchange factor, has been shown to activate GOA-1/Galpha0 in the ASH
chemosensory neurons to modulate behavior after food deprivation; full length AGS-3 binds
inactive GOA-1 (GOA-1-GDP) in pull down assays, while AGS-3 fragments containing the GPR
domains (also known as GoLoco domains) bind activated GOA-1 (GOA-1-GTP) in pull down
assays and GOA-1 in yeast two-hybrid assays; AGS-3 is expressed in all muscles, intestine, and
weakly in some head and ventral nerve cord neurons, with subcellular localization in strong dots; in
adults, an ags-3 reporter fusion is seen in nearly all neurons, including the ASH chemosensory
neurons, and in body wall muscle, egg-laying muscles, and pharyngeal muscles; AGS-3 subcellular
localization is regulated by food deprivation: AGS-3 moves from a Triton X-100 insoluble pellet
fraction to a Triton X-100 soluble pellet fraction after several hours of food deprivation.
ahr-1 encodes an aryl hydrocarbon receptor (ligand-activated basic helix-loop-helix transcription
factor) ortholog that biochemically resembles its vertebrate relatives (OMIM:600253) which
mediate the carcinogenic and teratogenic effects of environmental toxins; AHR-1 binds HSP90
tightly, and forms a dimer with AHA-1 that binds DNA fragments containing the mammalian
xenobiotic response element; AHR-1 is expressed in neurons, and may play a role in neuronal
migration.
alr-1 encodes a homeodomain transcription factor orthologous to aristaless/human Arx (OMIM:
300382); alr-1 regulates the development of sensory neurons in the head and GABAergic motor
neurons; ALR-1 affects TRN fate by acting as a transcriptional activator and is required selectively
for TRN gene expression; alr-1 expression in the TRNs depends on MEC-3; ALR-1 ensures TRN
differentiation by providing a second positive feedback circuit to maintain mec-3 expression; loss of
alr-1 produces variable touch sensation; alr-1 increases mec-3 expression by restricting mec-3
expression variability; alr-1 activity is needed throughout larval development; alr-1 is expressed in
the ALM, PLM, and AVM TRNs, but not in the nucleus of TRN PVM throughout all larval
development.
ant-1.4 encodes an ortholog of the human adenine nucleotide translocase ANT genes, the other ANT
genes in C. elegans include ant-1.1, ant-1.2 and ant-1.3; phylogenetic analysis indicates that ant-1.4
arf-1.2
arr-1
arf-1.2(ok1322)
RB1255
arf-1.2(ok796)
VC567
arr-1(ok401)
RB660
bbs-5
bbs-5(gk537)
VC1316
C24A8.
1
C24A8.1(ok2090)
RB1680
C29H12
.3
C29H12.3(ok228
8)
RB1780
cam-1
cam-1(ks52)
FK163
cav-1
cav-1(ok2089)
RB1679
cav-2
cav-2(hc191)
BA1090
ced-4
ced-4(n1162)
MT2547
is specific to C. elegans, resulting from a recent duplication following the speciation of the common
ancestor of C. elegans, C. briggsae, and C. remanei; by homology, ANT-1.4 is predicted to mediate
the exchange of ATP generated in the mitochondria for cytosolic ADP; ANT-1.4 GFP fusion protein
is expressed in a pair of head neurons, amphid socket and sheath cells and in a few body-wall
muscle and vulval muscle cells.
arf-1.2 encodes an ADP-ribosylation factor homolog required in vivo for embryonic development,
fertility, locomotion, vulval development, and cuticular synthesis; ARF proteins are N-myristoylated
GTPases that regulate membrane traffic and the actin cytoskeleton, and that activate both
phospholipase D1 (PLD1) and phosphatidylinositol 4-phosphate 5-kinase.
arr-1 encodes the C. elegans beta-arrestin ortholog (OMIM:107940, 107941, mice lacking betaarrestin family members display defects in G protein-coupled receptor desensitization); by
homology, ARR-1 is predicted to be a multifunctional adaptor protein that interacts with
intracellular signaling molecules as well as activated and phosphorylated G protein-coupled and
TGF-beta receptors to: 1) downregulate receptor signaling, 2) promote receptor endocytosis, and 3)
activate MAP kinase- and Src-dependent signaling pathways; in vivo, arr-1 activity is required for
normal egg laying and for proper olfactory adaptation and recovery to volatile odorants; in addition,
animals doubly mutant for arr-1 and grk-2, which encodes a G protein-coupled receptor kinase, are
sick and slow growing; ARR-1 is detected throughout the nervous system and is highly expressed in
the amphid chemosensory neurons; in neuronal cells, ARR-1 appears to be largely cytoplasmic;
ARR-1 interacts physically with clathrin and beta2-adaptin, two proteins involved in receptor
endocytosis.
bbs-5 encodes a novel protein that is the C. elegans ortholog of human BBS5 (OMIM:603650,
mutations in which are associated with Bardet-Biedl syndrome); a BBS-5::GFP reporter protein is
expressed exclusively in ciliated neurons, where it localizes to the ciliary base; consistent with the
presence of an X box in the bbs-5 5' UTR, bbs-5 expression is positively regulated by daf-19.
C24A8.1(ok2090)/dop-6 encodes an homolog of mammalian D2 or D3 dopamine receptors, and a
paralog of DOP-2/-3; dop-6 is expressed in the nervous system; because of its paralogy, DOP-6
might act redundantly with DOP-2 to promote the basal slowing response to bacterial feeding, or it
might account for the residual response to excess dopamine seen in triple dop-1/-2/-3 mutants; but
dop-6 otherwise has no obvious function in RNAi assays of brood size, egg laying, pharyngeal
pumping, locomotion, or male mating.
rgs-3 encodes three proteins containing two RGS (regulator of G protein signaling) domains, the
more C-terminal of which is most similar to those of the mammalian brain-specific RGS, RGS8;
rgs-3 activity is required for normal G protein-mediated response to a number of sensory stimuli,
including odorants, high osmolarity, and nose touch off food; genetic analyses indicate that RGS-3
functions to decrease G protein signaling in sensory neurons and increase glutamatergic synaptic
transmission from sensory to interneurons; RGS-3::GFP fusion proteins are expressed exclusively in
nine pairs of sensory neurons from late stages of embryogenesis through adulthood.
The cam-1 gene encodes a receptor tyrosine kinase of the immunoglobulin superfamily that is
orthologous to human ROR1 (OMIM:602336) and ROR2 (OMIM:602337, mutation of which leads
to type B brachydactyly) and is required for locomotion, cell migration, asymmetric cell division,
axon outgrowth, and dauer formation; CAM-1 is broadly expressed during embryogenesis and larval
development with expression first appearing at the 200-cell stage of embryogenesis.
cav-1 encodes one of two C. elegans caveolin orthologs; cav-1 is required for viability and
Ras/MAP-kinase-dependent progression through the meiotic cell cycle; CAV-1 is expressed in the
adult germ line and during embryonic development; CAV-1::GFP localizes to cortical granules that
function to secrete chondroitin and mucin-like proteoglycans to the extracellular space following
fertilization.
cav-2 encodes one of two C. elegans proteins related to caveolins, integral transmembrane proteins
that are believed to function in regulation of signal transduction and that are the major component of
caveolae, specialized lipid rafts found in the plasma membrane of most cell types; as loss of cav-2
function via large-scale RNA-mediated interference (RNAi) screens does not result in any obvious
abnormalities, the role of cav-2 in C. elegans development and/or behavior is not yet known; cav-2
mRNA is expressed in eggs and mixed stage populations.
ced-4 encodes a novel protein; along with CED-3, CED-4 is required for the initiation of
programmed cell death; accordingly, genetic analyses indicate that ced-3 and ced-4 function
upstream of ced-1, ced-2, and nuc-1 in the programmed cell death pathway; in yeast two-hybrid
experiments, and upon coexpression in mammalian cells, CED-4 interacts with CED-9, an antiapoptotic BCL-2 homolog; coexpression of CED-4 and CED-9 results in redistribution of CED-4
from the cytosol to organellar membranes, suggesting that CED-9 may negatively regulate CED-4
activity by sequestering CED-4 to intracellular membranes.
ceh-17
ceh-17(np1)
IB16
cfi-1
cfi-1(ky651)
OS122
chn-1
chn-1(by155)
BR2823
clh-6
clh-6(ok791)
RB920
cmk-1
cmk-1(oy21)
PY1589
cnx-1
cnx-1(nr2010)
NS2932
cri-2
cri-2(ok928)
RB1008
ctl-3
ctl-3(ok2042)
RB1653
ceh-17 encodes a phox-2-like homeodomain protein that is a member of the Q50 paired-like class of
homeobox proteins and the vertebrate orthologue of Phox2a and Phox2b; that affects ALA and SIA
axonal development; ceh-17 affects ALA and SIA antero-posterior axonal growth and navigation,
and is expressed in five neurons of the ring ganglia (ALA and the 4 SIAs) with strongest expression
in embryos and in L1 stage larvae.
cfi-1 encodes a DNA-binding protein containing an AT-rich interaction domain (ARID) that affects
differentiation of the URA sensory neurons, AVD, and PVC interneurons; acts downstream of UNC86 and LIN-32 in controlling URA and IL2 cell fate, and is expressed in some neurons and muscle
cells.
chn-1 encodes an ortholog of mammalian carboxyl-terminus of Hsc70 interacting protein (CHIP), an
E4 ubiquitin-chain elongation factor; chn-1 is ubiquitously expressed; chn-1(by155) mutants are
viable and superficially normal, but have reduced fertility and arrest as larvae if subjected to heat
shock; chn-1 overexpression causes either embryonic lethality (if strong) or defective egg-laying and
locomotion, along with constitutive dauer formation (if weak); chn-1(by155) mutations suppress
viable unc-45(e286ts) and unc-45(m94ts) mutations, but not lethal unc-45(st604) ones; chn1(by155) mutants, unlike wild-type, show defective sarcomeres if overexpressing unc-45 from a
extrachromosomal array; CHN-1 binds the ubiquitin conjugating enzyme UFD-2, which in turn
binds the Hsp90 cochaperone UNC-45; UNC-45 is a substrate for CHN-1- and UFD-2-dependent
multiubiquitination; the parkin ortholog PDR-1 binds CHN-1, and requires CHN-1 for selfubiquitination; chn-1(RNAi) animals accumulate abnormally phosphorylated tau proteins.
clh-6 encodes a voltage-gated chloride channel orthologous to the human CLCN7 chloride channel
(OMIM:602727, which when mutated lead to osteopetrosis); although the precise role of CLH-6 in
C. elegans development and/or behavior is not yet known, CLH-6 expression is detected in two
GABA-ergic neurons, RMEL and RMER, suggesting that CLH-6 could play a role in membrane
excitability and/or GABA packaging; as CLH-6 is also detected in many non-neuronal tissues, such
as the gut and body wall muscle, it could also have a broader role in such as processes as
transepithelial transport and muscle excitation.
cmk-1 encodes a Ca+2/calmodulin-dependent protein kinase I (CaMK1); CMK-1 activity is
required, cell autonomously and downstream of the cyclic nucleotide-gated channel TAX-4, for
several aspects of AFD thermosensory neuron differentiation, including expression of the gcy-8
guanylyl cyclase and nhr-38 nuclear hormone receptor genes and morphology of the AFD sensory
endings; cmk-1 activity is thus also required for normal thermosensory behavior; when expressed in
COS-7 cells, CMK-1 and CKK-1 positively regulate the transcriptional activity of endogenous
CREB; a cmk-1::gfp reporter is expressed in head sensory and interneurons as well as in the ventral
nerve cord; expression is seen specifically in the neurons of the thermosensory circuit, AFD, AIY,
and AIZ; in the AFD neurons, CMK-1 localizes exclusively to the cytoplasm, however when
expressed in COS-7 cells, CMK-1 is seen in the nucleus.
cnx-1 encodes the C. elegans ortholog of calnexin, a type I Ca2+-binding integral membrane protein
of the endoplasmic reticulum (ER); CNX-1 binds calcium and is predicted to function as a molecular
chaperone required for glycoprotein folding and maturation as well as regulation of intracellular
calcium homeostasis; in C. elegans, cnx-1 activity is required at 25 degrees C for wild-type levels of
fertility and normal embryonic and larval development; cnx-1 activity is also required for
maintaining viability in response to ER stress; in addition, cnx-1(RNAi) can suppress necrotic-like
cell death induced by hyperactivated MEC-4 and DEG-1 ion channels, suggesting that CNX-1 also
plays a role in regulating necrotic cell death; CNX-1 expression is first detected ubiquitously in the
early embryo, with expression then becoming restricted to embryonic head and tail regions; postembryonic expression is seen in the excretory cell, head and tail neurons, spermatheca, intestine,
germ cells, and spicules in the male tail; antibody staining of early embryos indicates that CNX-1
localizes to the endoplasmic reticulum; in regulating reproduction at 25 degrees C, cnx-1 functions
redundantly with crt-1, which encodes calreticulin, an additional Ca2+-binding ER chaperone
protein.
K07C11.5 is orthologous to the human gene similar to TISSUE INHIBITOR OF
METALLOPROTEINASE 3 (SORSBY FUNDUS DYSTROPHY, PSEUDOINFLAMMATORY)
(TIMP3; OMIM:188826), which when mutated leads to disease.
ctl-3 encodes one of three C. elegans catalases; CTL-3 is predicted to function as an antioxidant
enzyme that protects cells from reactive oxygen species; a ctl-3 promoter gfp fusion construct is
expressed in pharyngeal muscles and neuronal cell bodies; loss of ctl-3 activity via RNAi results in
no obvious abnormalities.
daf-1
daf-1(m40)
DR40
daf-10
daf-10(e1387)
CB1387
daf-11
daf-11(m47ts)
DR47
daf-12
daf-12(rh285)
AA85
daf-16
daf-16(mgDf50)
GR1307
daf-16(mu86)
CF1038
daf-19
daf-19(m86)
DR86
daf-2
daf-2(e1370)
CB1370
daf-2(m596)
DR1565
daf-22
daf-22(ok693)
RB859
daf-1 encodes a TGF-beta type I receptor homolog required, in association with the TGF beta-like
type II receptor DAF-4, for the regulation of dauer formation by environmental signals through the
ASI chemosensory neuron; DAF-1 is bound by BRA-1 and has an intracellular serine-threonine
kinase domain; mutations in daf-1 result in constitutive formation of dauer larvae even in abundant
food.
daf-10 encodes a WD- and WAA-repeat containing protein that is the C. elegans ortholog of
intraflagellar transport (IFT) complex A component IFT122; daf-10 activity is required for
intraflagellar transport and thus for proper development of amphid and phasmid neurons, dauer
development, chemotaxis, and normal lifespan; a DAF-10::GFP fusion protein undergoes both
anterograde and retrograde intraflagellar transport in amphid or phasmid sensory neurons.
daf-11 encodes a transmembrane guanylate cyclase; daf-11 activity is required for a number of
processes dependent upon normal chemosensory function, including dauer formation and recovery
and chemotaxis to both volatile and non-volatile odorants; daf-11 is also required for axon
formation; daf-11 acts together with daf-21 to regulate chemosensory function and genetically
upstream of daf-12 with respect to dauer larvae formation; in addition, daf-11 positively regulates
expression of daf-28 and daf-7, which encode insulin and TGF-beta signaling molecules,
respectively; a DAF-11::GFP fusion protein is expressed in a subset of amphid neurons where it
localizes to the ciliated sensory endings, the cell soma, and the dendrites.
daf-12 encodes a member of the steroid hormone receptor superfamily that is homologous to human
VITAMIN D RECEPTOR (VDR; OMIM:601769, mutated in vitamin D-resistant rickets); daf-12
affects dauer formation downstream of the TGF- and insulin signaling pathways, and affects gonaddependent adult longevity together with DAF-16, chemosensory signal transduction, and distal tip
cell migration and hypodermal and intestinal cell lineages during the L3 larval stage; DAF-12 is
expressed in the nucleus and in most cells; daf-12 expression in lateral seam cells is negatively
regulated by the let-7 miRNA.
daf-16 encodes the sole C. elegans forkhead box O (FOXO) homologue; DAF-16 functions as a
transcription factor that acts in the insulin/IGF-1-mediated signaling (IIS) pathway that regulates
dauer formation, longevity, fat metabolism, stress response, and innate immunity; DAF-16 regulates
these various processes through isoform-specific expression, isoform-specific regulation by different
AKT kinases, and differential regulation of target genes; DAF-16 can interact with the CBP-1
transcription cofactor in vitro, and interacts genetically with other genes in the insulin signaling and
with daf-12, which encodes a nuclear hormone receptor; DAF-16 is broadly expressed but displays
isoform-specific tissue enrichment; DAF-16 localizes to both the cytoplasm and the nucleus, with
the ratio between the two an important regulator of function.
daf-19 is the sole C. elegans member of the RFX family of transcription factors, and is required for
sensory neuron cilium formation; DAF-19 is expressed in ciliated sensory neurons during the period
that their cilia are generated, and probably functions as an common transcriptional activator of many
genes that specifically encode cilial structures in sensory neurons; daf-19 mutants lack sensory cilia,
have abnormal amphids, are strongly dauer-constutive, lack normal openings of the amphids to the
external environment (i.e., fail to show dye-filling), and are highly defective in their ability to taste
or smell; DAF-19 regulates bbs-5, che-2, che-13, dyf-3, osm-1, osm-6, and xbx-1 expression, and
probably regulates ~200 other genes (e.g., bbs-2, bbs-7 and bbs-8); the localization of DAF-6 is
aberrant in daf-19 mutants.
daf-2 encodes a receptor tyrosine kinase that is the C. elegans insulin/IGF receptor ortholog; DAF-2
activity is required for a number of processes in C. elegans, including embryonic and larval
development, formation of the developmentally arrested dauer larval stage (diapause), larval
developmental timing, adult longevity, reproduction, fat storage, salt chemotaxis learning, and stress
resistance, including response to high temperature, oxidative stress, and bacterial infection; DAF-2
signals through a conserved PI 3-kinase pathway to negatively regulate the activity of DAF-16, a
Forkhead-related transcription factor, by inducing its phosphorylation and nuclear exclusion; in
addition, DAF-2 negatively regulates the nuclear localization, and hence transcriptional activity, of
SKN-1 in intestinal nuclei; amongst the 38 predicted insulin-like molecules in C. elegans, genetic
and microarray analyses suggest that at least DAF-28, INS-1, and INS-7 are likely DAF-2 ligands;
genetic mosaic and tissue-specific promoter studies indicate that daf-2 can function cell
nonautonomously and within multiple cell types to influence dauer formation and adult lifespan,
likely by regulating the production of secondary endocrine signals that coordinate growth and
longevity throughout the animal; temporal analysis of daf-2 function indicates that daf-2 regulates
lifespan, reproduction, and diapause independently, at distinct times during the animal's life cycle.
daf-22 encodes the C. elegans ortholog of human sterol carrier protein SCP2, which catalyzes the
final step in peroxisomal fatty acid beta-oxidation; in C. elegans, DAF-22 activity is required for
daf-3
daf-3(e1376)
CB1376
daf-3(mgDf90)
GR1311
daf-4
daf-4(e1364)
CB1364
daf-6
daf-6(e1377)
CB1377
dbl-1
dbl-1(nk3)
NU3
dgk-1
dgk-1(nu199)
KP828
dgk-1(sy428)
PS2627
dgk-3
dgk-3(gk110)
VC218
dauer pheromone biosynthesis; daf-22 mutant animals cannot produce dauer pheromone, but can
synthesize weakly active longer-chain fatty acid derivatives; in synthesizing dauer pheromone,
DAF-22 acts downstream of DHS-28, the C. elegans ortholog of human HSD17B4 (hydroxysteroid
(17-beta) dehydrogenase 4); a DAF-22::GFP fusion protein is expressed in a punctate pattern in the
intestine, hypodermis, and body wall muscle throughout the life cycle; DAF-22 expression in the
intestine is sufficient to produce dauer pheromone.
daf-3 encodes a co-SMAD protein that is most closely related to Drosophila Medea and the
vertebrate Smad4 proteins; DAF-3 functions as a transcriptional regulator that is required for
formation of the alternative dauer larval stage as well as for regulation of pharyngeal gene
expression during non-dauer development; DAF-3 activity is antagonized by signaling through the
DAF-7/TGF-beta pathway which promotes reproductive growth; in yeast two-hybrid studies, DAF-3
interacts with SMA-3, another Smad protein that does not appear to have a role in dauer formation;
in vitro, DAF-3 binds the organ-specific C subelement in the promoter of the pharyngeal musclespecific myosin myo-2 and in vivo, suppresses the enhancer activity of this element during larval
development; a DAF-3::GFP fusion protein is expressed in many tissues that undergo remodeling
during dauer development, including the gut, nervous system and pharynx; DAF-3 localizes
predominantly to the cytoplasm, but is also found in the nucleus in association with mitotic
chromosomes.
daf-4 encodes a transmembrane serine/threonine kinase that is the sole C. elegans ortholog of the
type II transforming growth factor-beta (TGF-b) receptors; DAF-4 activity is required for several
biological processes, including entry into and exit from the dauer larval stage, body size
determination, male tail patterning, egg laying, chemosensory neuron specification, and increased
thermotolerance; in regulating dauer larval development, DAF-4 acts in parallel with the insulin
signaling pathway and likely partners with the DAF-1 type I TGF-b receptor to receive a signal from
the DAF-7 TGF-b ligand; in body size determination and male tail patterning, DAF-4 likely partners
with the SMA-6 type I receptor and responds to signals from the DBL-1 ligand; thus daf-4 is utilized
by both the Dauer TGF-beta pathway and the TGF-beta Sma/Mab pathway; daf-4 also regulates
reproductive aging, via the TGF-beta Sma/Mab pathway, mutants of which show a large
reproductive span extension; DAF-4 expression begins in late embryogenesis and continues through
larval and adult stages; consistent with its role in many developmental processes, DAF-4 localizes to
the plasma membrane of several tissues including head and tail neurons, the pharynx, intestine,
ventral nerve cord, tail hypodermis, and body wall muscle.
daf-6 encodes a Patched-related protein; daf-6 is required for amphid channel morphogenesis and
thus, also for normal morphology of the outer labial sensilla; specifically, daf-6 is required for
restricting the amphid sensory compartment diameter; daf-6 mutants display defects in several
neuron-mediated functions including dauer larvae formation, chemotaxis, osmotic avoidance, male
mating, negative regulation of lifespan, negative regulation of the neuron ASJ's axonal growth late
in development, and dye uptake by amphids and phasmids; a DAF-6::GFP is expressed in the
amphid sheath and socket cells and in the excretory canal.
dbl-1 encodes a member of the transforming growth factor beta (TGFbeta) superfamily that includes
Drosophila decapentaplegic (Dpp) and the vertebrate bone morphogenetic proteins (BMPs); DBL-1
functions as a dose-dependent ligand for the SMA-6 and DAF-4 TGFbeta receptors that ultimately
activate the SMA-2, -3, and -4 complex of transcription factors to regulate body length and size, as
well as the patterning of male sensory rays and copulatory spicules; DBL-1 signaling upregulates
sma-6 expression, suggesting that there is positive autoregulation in the DBL-1 signaling pathway;
in contrast, DBL-1 negatively regulates expression of LON-1, a predicted secreted protein that is a
downstream component of the body size pathway; in addition to its other roles, the TGFbeta
Sma/Mab pathway also regulates reproductive aging, mutants of the pathway show an extension of
the reproductive span, independent of somatic longevity; DBL-1 is expressed primarily in neurons.
dgk-1 encodes an ortholog of mammalian diacylglycerol kinase theta (DGKQ); dgk-1 activity
functions downstream in a serotonin signaling pathway that regulates locomotion and synaptic
transmission; in addition, dgk-1 activity negatively regulates egg laying; dgk-1 genetically interacts
with the goa-1 and egl-30 signaling pathways; a GFP::DGK-1 reporter fusion protein is expressed in
the excretory canals and in most neurons, including the ventral cord neurons; in neurons,
GFP::DGK-1 localizes to axons and cell bodies; when expressed ectopically in HEK293 cells,
DGK-1 exhibits DAG kinase activity.
dgk-3 encodes a diacylglycerol kinase that is the C. elegans ortholog of mammalian DGK-beta; dgk3 activity is required for regulation of long-term thermotactic behavioral plasticity and for regulation
of olfactory adaptation; large-scale expression studies have reported dgk-3 expression in head
neurons, the intestine, and the pharyngeal lumen, while expression profiling indicates that dgk-3 is
dgk-4
dgk-4(ok1031)
RB1073
dhc-1
dhc-1(or283ts)
EU1385
din-1
din-1(dh127)
AA408
dop-3(vs106)
LX703
dop-3
dop-4
drp-1
dop-4(tm1392)
FG58
drp-1(tm1108)
CU6372
dsh-1
dsh-1(ok1445)
RB1328
dyb-1
dyb-1(cx36)
LS505
dyf-5(hc183)
BA1073
dyf-5
dys-1
eat-16
dys-1(cx18)
LS292
eat-16(sy438)
PS2960
eat-2
eat-2(ad465)
DA465
eat-4
eat-4(ky5)
MT6308
expressed in the AFD thermosensory neurons as well as a small number of additional sensory
neurons.
dgk-4 encodes a diacylglycerol kinase (DGK) that is most closely related to the mammalian DGK
subfamily that includes DGKH and DGKD; in situ hybridization studies have detected dgk-4 mRNA
in the gonad, and large-scale expression studies have reported expression in a wide range of tissues
including hypodermis, muscle, neurons, and the pharynx.
dhc-1 encodes a cytoplasmic dynein heavy chain homolog required in one-cell embryos for
pronuclear migration, centrosome separation, centrosome proximity to the male pronucleus, and
mitotic spindle orientation, suggesting that DHC-1 helps position the microtubule organizing center;
DHC-1 genetically interacts with SPD-5, a coiled-coil centrosomal protein.
DAF-12 Interacting Protein
dop-3 encodes a homolog of mammalian D2 dopamine receptors that is required for the normal
slowing of locomotion by well-fed animals moving onto a bacterial lawn ('basal slowing'), but not
for the enhanced slowing of starved animals ('enhanced slowing response'); DOP-3 is also required
for the paralysis of animals by excess dopamine, with dop-3 mutants showing significant resistance
to such paralysis; DOP-3 is antagonized by DOP-1 (since a dop-1 mutation suppresses the dop-3
slowing and paralysis mutant phenotypes); DOP-3 and DOP-1 are coexpressed in cholinergic motor
neurons and PVD mechanosensory neurons, and exert their antagonistic effects in the former; DOP3 is also expressed in neurons of the head and tail; dop-3 mutants share a dopamine-resistant
phenotype with goa-1, dgk-1, eat-16 and gpb-2 mutants; DOP-3 and DOP-1 probably counter one
another through the GOA-1/Galpha(o) and EGL-30/Galpha(q) signaling pathways.
DOPamine receptor
drp-1 encodes a dynamin-related protein, orthologous to Dnm1p in S. cerevisiae and DRP1 in
mammals, that is required for severing of the mitochondrial outer membrane during mitochondrial
division.
dsh-1 encodes a homolog of Drosophila DISHEVELED and a paralog of MIG-5 (and DSH-2);
DSH-1 appears to be required for Wnt-induced endoderm specification in the EMS blastomere, and
may influence HSN migration as well.
The dyb-1 gene encodes a homolog of mammalian alpha-dystrobrevin (DTNA; OMIM:601239),
mutation of which can lead to left ventricular noncompaction with congenital heart defects.
dyf-5 encodes a putative MAP kinase orthologous to human MAK/ICK (OMIM:154235),
Chlamydomonas reinhardtii LF4, and Leishmania mexicana MPK9; DYF-5 negatively regulates
cilial length, restricts KAP-1 to middle ciliary segments, is required for normal localization of six
IFT components, and is required for OSM-3 to comigrate normally with IFT particles; DYF-5 is also
required for dye-filling of amphid and phasmid neurons and for normal chemotaxis, dauer
formation, and male mating; DYF-5 is expressed in head neurons (including amphid neurons), tail
neurons (including phasmid neurons), CAN cells, excretory canal neurons, posterior lateral ganglion
neurons and in many male tail cells; dyf-5 mutant cilia are abnormally elongated, either failing to
enter the amphid channel or accumulating IFT proteins at their distal ends, whereas DYF-5
overexpression results in truncated cilia; the dyf-5 promoter region contains an X-box, predicted to
be bound and transcriptionally activated by DAF-19, and dyf-5 is regulated by DAF-19 in vivo; dyf5 animals are slightly shorter than normal.
The dys-1 gene encodes an ortholog of human DMD, which when mutated leads to Duchenne
muscular dystrophy (OMIM:310200).
The eat-16 gene encodes an RGS protein that affects movement, pharyngeal pumping, egg laying,
and synaptic transmission; it genetically interacts with the egl-30 and goa-1 signaling pathways, and
is expressed in excitable cells and in the spermatheca.
eat-2 encodes a ligand-gated ion channel subunit most closely related to the non-alpha-subunits of
nicotinic acetylcholine receptors (nAChR); EAT-2 functions postsynaptically in pharyngeal muscle
to regulate the rate of pharyngeal pumping; eat-2 is also required for normal life span and
defecation; a functional EAT-2::GFP fusion protein localizes to two small dots near the junction of
pharyngeal muscles pm4 and pm5, which is the site of the posterior-most MC motor neuron
processes and the MC synapse; eat-2 genetically interacts with eat-18, which encodes a predicted
novel transmembrane protein expressed in pharyngeal muscle and required for proper function of
pharyngeal nicotonic receptors.
eat-4 encodes an ortholog of the mammalian BNPI vesicular glutamate transporter that affects
chemotaxis, feeding, foraging and thermotaxis; eat-4 is expressed in specific neurons, including
M3L and M3R which are known to be glutamatergic.
ect-2
ect-2(ku427)
MH2407
egl-10
egl-10(md176)
MT8504
egl-2
egl-2(n693)
MT1444
egl-21
egl-21(n476)
MT1071
egl-3
egl-3(n150)
MT150
egl-30(ad809)
PS3202
egl-30
egl-8
egl-8(n488)
MT1083
eri-1
eri-1(mg366)
GR1373
exp-1
exp-1(sa6)
JT6
F11C7.1
F11C7.1(ok1564)
RB1379
ect-2 encodes, by alternative splicing, two isoforms of a putative RHO guanine nucleotide exchange
factor (RhoGEF) required for cytokinesis of early embryos and epidermal P cells, as well as cell
polarity of early embryos and migration of epidermal P cells; ECT-2 is thus required for normal
vulval differentiation and locomotion, along with fertility and embryonic viability; ECT-2 also
activates LET-60/RAS signalling during vulval development, requiring RHO-1 to do so; ECT-2 is
orthologous to the proto-oncogene ECT2 (OMIM:600586) and Drosophila PEBBLE; ECT-2 has
two BRCT domains and a RhoGEF domain; ect-2 is expressed ubiquitously during embryogenesis,
but restricted to Q cells in early L1 larvae; ect-2's expression then broadens to P-cell derivatives and
distal tip cells, vulval precursor cells and their derivatives, and some adult neurons; ECT-2 is
symmetrically distributed in unfertilized oocytes, but then temporarily becomes asymmetrically
depleted around the centrosomal protein SPD-5, and is required for initial anteroposterior
polarization of the newly fertilized embryo; anterior localization of PAR-6 in newly fertilized
embryos requires ECT-2, which colocalizes with the nonmuscle myosin NMY-2 in the early
embryonic cell cortex; the boundary of anterior versus posterior domains in the early embryo
depends on the antagonistic activities of ECT-2 versus RGA-3/4; a hypomorphic ect-2 mutation
suppresses the multivulva phenotype of lin-32, whereas a gain-of-function ect-2 mutation
hyperinduces vulval development; ECT-2 is expressed in embryonic and P cells.
egl-10 encodes an RGS protein, expressed in neurons, that affects egg laying and negatively
regulates GOA-1 (Galpha[o]) signalling; it requires the Gbeta(5) ortholog GPB-2 for this activity,
and genetically interacts with the egl-30 and goa-1 signaling pathways.
egl-2 encodes a voltage-gated potassium channel that is the C. elegans homolog of ether-a-go-go
(EAG); egl-2 activity is required for egg laying, muscle activation, defecation, mechanosensation,
and chemosensation; egl-2 is expressed in the intestinal muscle, AFD, ALN, AQR, ASE, AWC,
BAG, IL2, PLN, PQR, and URX neurons as well as a subset of sensory neurons in the male tail;
EGL-2 activity can be regulated by the UNC-43 calcium/calmodulin-dependent protein kinase II
(CaMKII) with which it interacts physically.
egl-21 encodes a putative carboxypeptidase (whose homologs include human enkephalin
convertase/carboxypeptidase E); EGL-21 is expressed throughout the nervous system; EGL-21 is
required for normal synthesis of FMRFamide-like (FLP) and neuropeptide-like (NLP) peptides, and
for normal egg-laying, locomotion, and defecation; EGL-21 promotes acetylcholine release at
neuromuscular junctions; egl-21 mutant defects resemble those seen for mutants of the proprotein
convertase type 2 EGL-3.
The egl-3 gene encodes a homolog of a mammalian proprotein convertase that participates in
peptide secretion.
egl-30 encodes an ortholog of the heterotrimeric G protein alpha subunit Gq (Gq/G11 class) that
affects viability, locomotion, egg laying, synaptic transmission, and pharyngeal pumping; it
genetically interacts with the goa-1 pathway, and is probably expressed ubiquitously, with highest
expression in excitable cells.
egl-8 encodes a phospholipase C beta homolog that affects pharyngeal pumping, defecation, and
activity levels; it is genetically downstream of egl-30 with respect to aldicarb-induced paralysis, and
is expressed in most or all neurons, with the strongest staining in the head and tail ganglia, and in the
intestine.
eri-1 encodes a conserved RNAse that contains a SAP/SAF box domain and a DEDDh-like 3'-5'
exonuclease domain; eri-1 activity is required for negative regulation of RNA interference as well as
for normal sperm function at high temperatures and proper meiotic chromosome segreation; in vitro,
ERI-1 demonstrates exonuclease activity against siRNAs with 2-nt 3' overhangs, consistent with
genetic analyses suggesting that, in vivo, eri-1 activity depends upon formation of siRNAs by the
canonical RNAi pathway; an ERI-1::GFP reporter fusion protein is expressed in a subset of neurons
and in the spermatheca and localizes mainly to the cytoplasm; eri-1::gfp promoter fusions also
reveal low ubiquitous expression throughout the animal.
exp-1 encodes an excitatory, cation-selective GABA receptor; EXP-1 activity is essential for the
enteric muscle contractions that are the third in a series of three independent muscle contractions
controlling defecation, and when expressed in Xenopus oocytes, EXP-1 is capable of forming a
cation-selective GABA receptor; a rescuing EXP-1::GFP reporter fusion is expressed in the
intestinal and anal depressor muscles, where it localizes to regions consistent with the positions of
neuromuscular junctions; expression is also observed in neurons, including PDA, RID, ADE, and
SABD.
pbo-6/lgc-3 encodes a proton-gated ion channel which has no known function, but that is thought to
form functional heterodimers with PBO-5/LGC-2; PBO-6 has no obvious non-nematode orthologs,
but is paralogous to PBO-5; while heterologous PBO-6 has no activity when expressed in Xenopus
F46F6.2
flp-1
F46F6.2(ok1673)
VC1414
flp-1(yn2)
NY7
flp-10
flp-10(ok2624)
RB1989
flp-16
flp-16(ok3085)
RB2275
flp-20(ok2964)
RB2188
flp-25(gk1016)
VC1982
flp-7(ok2625)
RB1990
flp-20
flp-25
flp-7
flp-9
flp-9(ok2730)
RB2067
fox-1
fox-1(e2643)
CB5380
fre-1
fre-1(ok756)
RB897
frm-8
frm-8(ok1769)
RB1501
fsn-1(gk429)
VC980
fzo-1(tm1133)
CU5991
fsn-1
fzo-1
gar-1
gar-1(ok755)
RB896
gar-2
gar-2(ok520)
RB756
oocytes, it produces strong currents when coexpressed with PBO-5 and stimulated by pH 6.0; PBO6 is expressed in the most posterior bodywall muscles; unlike pbo-5 mutants, pbo-6(ok1564)
mutants and pbo-6(RNAi) animals have no obvious phenotypes.
Protein Kinase N (PKN) homolog
flp-1 can encode up to seven distinct, yet highly similar, FMRFamide-related peptides (FaRPs),
small neuromodulatory peptides that are characterized by a C-terminal Arg-Phe-amide motif; in C.
elegans, FLP-1 peptides are required for regulation of several behaviors, including well-coordinated,
sinusoidal movement and the transition between active and inactive states of egg-laying; receptors
for the FLP-1 peptides have not yet been identified, but genetic studies indicate that FLP-1 peptides
may act through G-protein coupled receptors; flp-1 mRNAs are detected at all developmental stages,
and a FLP-1 translational reporter fusion detects expression in the anteriorly positioned neurons
AVK, AVA, AVE, RIG, RMG, AIY, AIA, and M5
flp-10 encodes a FMRFamide-related neuropeptide; in males, flp-10 activity is required for a
sensory transduction pathway that negatively regulates the frequency of certain substeps of turning
behavior during mating; a flp-10::gfp reporter is expressed in a number of neurons including AIM,
ASI, AUA, BAG, BDU, DVB, PQR, PVR, and URX, and in the vulD cells.
flp-16 encodes a predicted FMRFamide-like peptide neurotransmitter that inhibits action potentials
in the pharyngeal muscle when applied to the pharynx of dissected worms.
flp-20 encodes two copies of a single FMRFamide-related short peptide neurotransmitter; the
precise role of this peptide in C. elegans neurotransmission is not yet known.
FMRF-Like Peptide
flp-7 encodes an MVRFamide-containing peptide that, upon injection into A. suum, produces
paralysis and loss of locomotory waveforms, increased body length, and decreased cAMP
production.
flp-9 encodes a predicted FMRFamide-like peptide neurotransmitter that inhibits action potentials in
the pharyngeal muscle when applied to the pharynx of dissected worms and inhibits movement
when injected into A. suum; expressed at highest levels prior to adulthood.
fox-1 encodes an RNA-binding protein of the RNA recognition motif (RRM) superfamily of
ribonucleic acid binding proteins; during C. elegans development, FOX-1 functions redundantly
with other numerator elements to effect proper dosage compensation in the early embryo; in
influencing dosage compensation, FOX-1 likely acts via post-transcriptional regulation of xol-1
mRNA levels; in addition to its role in dosage compensation, fox-1 activity is also required for
normal male mating behavior; Western analysis and lacZ reporter constructs indicate that FOX-1 is
expressed throughout the life cycle, beginning at the 18-20-cell stage of embryogenesis and
continuing on through larval stages and into adult hermaphrodites and males; while early embryonic
expression of fox-1 is ubiquitous, postembryonic expression is limited to a subset of head and tail
neurons.
fre-1 encodes an NADPH-dependent flavin reductase; fre-1 is the downstream gene in an operon
with dcs-1, which encodes a scavenger mRNA decapping enzyme; reporter fusions using dcs-1
upstream sequence direct expression throughout the life cycle in neurons and pharyngeal muscle;
expression is present in dauer larvae and enhanced by heat shock.
frm-8 encodes a protein containing a WW domain, a PDZ domain, and a FERM domain and has
homology to the human predicted protein KIAA0316.
fsn-1 encodes a protein containing an F-box, a motif predicted to mediate protein-protein
interactions either with homologs of yeast Skp-1p or with other proteins
fzo-1 encodes a GTPase orthologous to MFN1(Mitofusin)/FZO1, a conserved mitochondrial
transmembrane protein essential for mitochondrial fusion; in C. elegans, fzo-1 is also required for
mitochondrial fusion and organization and accordingly, is essential for reproduction, embryonic
development, and normal growth rates.
gar-1 encodes a G-protein-linked acetylcholine receptor; though gar-1 is most closely related to
muscarinic acetylcholine receptors (mAChR), it is pharmacologically distinct from them in its
response to certain ligands; gar-1 gene transcripts are expressed at all developmental stages; the
GAR-1-GFP fusion protein is expressed in some head neurons and in the PVM neuron;
electrophysiological studies indicate that gar-1 couples to the inhibitory subunit of G proteins and
not to Gs or to Go/Gq.
gar-2 encodes a novel, seven transmembrane-domain G protein-coupled acetylcholine receptor
(AChR); when expressed in Xenopus oocytes treated with acetylcholine, GAR-2 is able to activate a
mammalian G protein-activated inwardly rectifying K+ (GIRK1) channel, but not other channels,
gar-3
gar-3(gk305)
VC657
gcy-18
gcy-18(nj38)
IK429
gcy-5
gcy-5(ok930)
RB1010
glr-1(n2461)
KP4
glr-1
goa-1
goa-1(sy192)
PS1762
gpa-10
gpa-10(pk362)
NL1147
gpa-6(pk480)
NL1146
gpa-6
gpa-7
gpa-8
gpb-2
gpc-1
grd-7
gpa-7(pk610)
NL795
gpa-8(pk345)
NL1142
gpb-2(sa603)
JT603
gpc-1(pk298)
NL792
grd-7(ok3395)
RB2456
suggesting that GAR-2 couples to G proteins of the Gi family; pharmacological analyses indicate,
however, that GAR-2 exhibits properties distinct from mammalian muscarinic AChRs; gar-2 is
expressed from mid-embryogenesis through adulthood with expression seen in ciliated head
neurons, ventral cord neurons, and the HSN (hermaphrodite-specific neuron).
gar-3 encodes a muscarinic acetylcholine receptor; gar-3 activity is required for regulation of
membrane potential and excitation-contraction coupling in pharyngeal muscle and thus, for normal
feeding behavior; in regulating pharyngeal pumping, GAR-3 likely acts upstream of GPB-2, a Gprotein beta-subunit; a gar-3::gfp reporter fusion is expressed in the I3 pharyngeal neuron,
extrapharyngeal neurons, and in pharyngeal muscles, where expression is highest in the terminal
bulb.
gcy-18 encodes a receptor-type guanylyl cyclase that, along with gcy-8 and gcy-23, constitutes a
subfamily of guanylyl cyclase genes in C. elegans; gcy-18 functions redundantly with gcy-8 and
gcy-23, and upstream of tax-4, to regulate thermotaxis via the AFD thermosensory neurons,
although of the three guanylyl cyclases required, genetic analyses suggest that GCY-18 is the
primary guanylyl cyclase required; in addition, microarray experiments indicate that gcy-18
expression is induced in daf-16(RNAi); daf-2(RNAi) double mutants and repressed in daf-2(RNAi)
mutants, suggesting that GCY-18 activity may contribute to a shortened lifespan; consistent with
this, loss of gcy-18 activity via RNAi does result in lifespan extension; GCY-18 is expressed
exclusively in the AFD thermosensory neurons, where it localizes to sensory endings.
gcy-5 encodes a predicted guanylate cyclase with strong similarity to rat atrial natriuretic peptide
receptor A; expressed in ASER.
glr-1 encodes an AMPA-type ionotropic glutamate receptor subunit; GLR-1 activity is required for
mediating the behavioral response to light nose touch and the frequency with which animals change
locomotory direction in response to sensory cues such as food; GLR-1 and GLR-2, a second AMPAtype ionotropic glutamate receptor, can interact to form functional heteromeric channels; GLR-1 is
expressed in motorneurons and interneurons, including four of the five pairs of command
interneurons that are required for locomotory control; in the ventral nerve cord and nerve ring, GLR1 localizes to perinuclear structures in cell bodies and to punctate structures that appear to be
glutamatergic postsynaptic specializations; proper GLR-1 localization in the anterior ventral nerve
cord of older larvae and adults requires activity of the class I PDZ protein LIN-10; GLR-1 is
ubiquitinated in vivo and its abundance at postsynaptic elements, which may influence postsynaptic
strength, is regulated by ubiquitination; indeed, GLR-1 trafficking in interneurons has been shown to
be regulated by the UEV-1 ubiquitin-conjugating enzyme variant and the UBC-13 ubiquitinconjugating enzyme.
goa-1 encodes an ortholog of the heterotrimeric G protein alpha subunit Go (Go/Gi class); GOA-1
activity is required for regulation of a number of behaviors, including locomotion, egg-laying, male
mating, and olfactory-mediated behaviors; GOA-1 activity is also required for asymmetric cell
division in the early embryo; goa-1 genetically interacts with the egl-30 pathway, and is expressed in
all neurons and sex-specific muscles; GOA-1 physically interacts with RIC-8 and AGS-3, and its
activity is modulated by RIC-8 and RGS-7 in in vitro assays.
gpa-10 encodes a member of the G protein alpha subunit family of heterotrimeric GTPases; it is
expressed in ADF, ASI, ASJ, ALN, CAN, LUA, and the spermatheca.
gpa-6 encodes a member of the G protein alpha subunit family of heterotrimeric GTPases that
affects response to water-soluble odorants; it is expressed in AWA amphid neurons, the PHB
sensory cell, and (at low levels) in ASI amphid neurons.
gpa-7 encodes a member of the G protein alpha subunit family of heterotrimeric GTPases that
affects egg laying and response to water- soluble odorants; it is expressed in excitable cells.
gpa-8 encodes a member of the G protein alpha subunit family of heterotrimeric GTPases; expressed
in URX, AQR, and PQR sensory cells.
gpb-2 encodes an ortholog of Gbeta(5), that is dispensable for viability, but required for normal egglaying, locomotion, and pharyngeal pumping; GBP-2 may regulate the interaction between the
GOA-1 and EGL-30 signaling pathways based on genetic analysis; gpb-2 is expressed throughout
development in the nervous system and in muscle, and expression is dependent upon expression of
both EAT-16 and EGL-10.
The gpc-1 gene encodes a heterotrimeric guanine nucleotide-binding protein gamma subunit,
expressed specifically in sensory neurons, that is involved in taste adaptation.
grd-7 encodes a hedgehog-like protein, with an N-terminal DUF271 domain, a central lowcomplexity proline-rich domain, and a C-terminal Ground (Grd) domain; GRD-7 is expressed in
three to four posterior DA motor neurons of the ventral nerve cord; the Ground domain is predicted
to form a cysteine-crosslinked protein involved in intercellular signalling, and it has subtle similarity
grl-4
grl-4(ok1076)
RB1097
hbl-1
hbl-1(mg285)
CT11
hlh-34
hlh-34(gk1031)
VC1904
hsp-3(ok1083)
RB1104
hsp-3
ida-1
ida-1(ok409)
VC226
ife-2
ife-2(ok306)
KX15
ife-4(ok320)
KX17
ins-30(ok2343)
RB1809
ins-4(ok3534)
RB2544
ins-6(tm2416)
FX02416
inx-10(ok2714)
RB2051
ife-4
ins-30
ins-4
ins-6
inx-10
inx-11
inx-14
inx-19
inx-2
inx-11(ok2783)
RB2108
inx-14(ag17)
AU98
inx-19(ky634)
CX6161
inx-2(ok376)
VC260
to the N-terminal Hedge domain of HEDGEHOG proteins; GRD-7 is weakly required for normal
molting; GRD-7 is also required for normal growth to full size, cuticle adhesion, locomotion, and
vulval morphogenesis; all of these requirements may reflect common defects in cholesteroldependent hedgehog-like signalling or in vesicle trafficking.
grl-4 encodes a hedgehog-like protein, with an N-terminal signal sequence, a central proline-rich
low-complexity region, and a C-terminal Ground-like (Grl) domain; GRL-4 is expressed in pharynx,
reproductive system, vulva, larval neurons, and larval rectal epithelium; the Grl domain is predicted
to form a cysteine-crosslinked protein involved in intercellular signalling, and it has subtle similarity
to the N-terminal Hedge domain of HEDGEHOG proteins.
hbl-1 encodes a C2H2-type zinc finger transcription factor related to Drosophila hunchback; hbl-1 is
a heterochronic gene that plays an essential role in regulating developmental timing during
postembryonic development; accordingly, mutations in hbl-1 affect locomotion, egg laying, body
morphology, and hypodermal differentiation; hbl-1 is expressed in hypodermal precursor cells,
neuronal precursor cells, and pharyngeal cells during embryogenesis and is primarily expressed in
neurons during larval development; hbl-1 expression is negatively regulated by the let-7 miRNA
whose expression is, in turn, negatively regulated by HBL-1 in a negative feedback loop.
Helix Loop Helix
hsp-3 encodes one of two C. elegans heat shock response 70 (hsp70) proteins homologous to
mammalian grp78/BiP (glucose regulated protein 78/immunoglobulin heavy chain-binding protein,
OMIM:138120); HSP-3 likely functions as a molecular chaperone, and is expressed constitutively
(expression is not heat inducible) throughout development with greatest abundance during the L1
larval stage; hsp-3 transcription is, however, upregulated in response to endoplasmic reticulum stress
induced by dithiothreitol (DTT) or tunicamycin; HSP-3 contains a long hydrophobic amino terminus
and a carboxyl terminal KDEL sequence suggesting that it may be retained in the endoplasmic
reticulum.
ida-1 encodes a protein tyrosine phosphatase-like receptor, orthologous to the mammalian type I
diabetes autoantigens IA-2 and phogrin that are expressed in dense core vesicles of neuroendocrine
tissue and involved in regulated protein secretion; in C. elegans, IDA-1 appears to be required for
regulating presynaptic neurotransmission and in particular, for the neuropeptidergic control of egglaying; ida-1 interacts genetically with unc-31 and unc-64, which encode proteins required for dense
core vesicle fusion and exocytosis; ida-1 expression is detected in a subset of neurons in the anterior
nerve ring, the ventral nerve cord, the tail, and the vulva, including the VC vulval motoneurons and
the HSN egg-laying neurons; ida-1 is also detected in the vulval uv1 cells, non-neuronal cells that
contain neurosecretory-like vesicles.
The ife-1 gene encodes one of five C. elegans homologs of the mRNA cap-binding protein eIF4E; it
is specifically required for spermatogenesis, and is expressed in P granules.
The ife-4 gene encodes a member of the Initiation Factor 4E (eIF4E) family.
ins-30 encodes an insulin-like peptide.
ins-4 encodes an insulin-like peptide.
ins-6 encodes predicted type-beta insulin-like molecule that lacks a C peptide domain; expressed
throughout development and in some neurons beginning in the two-fold elongated embryo.
inx-10 encodes an innexin, an integral transmembrane channel protein that is a structural component
of invertebrate gap junctions; as loss of INX-10 function via RNA-mediated interference (RNAi)
does not result in any abnormalities, the precise role of INX-10 in C. elegans development and/or
behavior is not yet known; INX-10 is broadly expressed and detected in the developing embryonic
pharynx and in larvae and adults in the pharyngeal corpus and terminal bulb, the sheath, several
ventral cord neurons, rectal epithelial cells, the developing spermathecum, and in a few vulval cells.
inx-11 encodes a predicted member of the innexin family; expressed in the pharynx, a few head
neurons, the tail hypodermis, posterior intestine and in some vulval and uterine muscles.
inx-14 encodes a predicted member of the innexin family that affects embryonic viability and
fertility.
inx-19 encodes an innexin, proteins that form gap junction channels; inx-19 functions in parallel
with the NSY-4 claudin to specify the AWC chemosensory neuron ON fate; in specifying the AWC
on fate, inx-19 appears to function cell autonomously; inx-19 also regulates body size and growth.
INneXin
inx-20
inx-21
inx-22
inx-4
inx-5
inx-6
inx-7
inx-8
ipp-5
inx-20(ok681)
RB851
inx-21(ok2524)
CB1929
inx-22(tm1661)
XM1011
inx-4(ok2373)
RB1834
inx-5(ok1053)
RB1086
inx-6(rr5)
MR127
inx-7(ok2319)
RB1792
inx-8(gk42)
VC116
ipp-5(sy605)
PS3653
isp-1
isp-1(qm150)
MQ887
itr-1
itr-1(sa73)
JT73
jkk-1
jkk-1(km2)
KU2
jnk-1
jnk-1(gk7)
VC8
lev-8
lev-8(ok1519)
VC1041
lim-6
lim-6(nr2073)
OH110
INneXin
inx-21 encodes an innexin, an integral transmembrane channel protein that is a structural component
of invertebrate gap junctions; as loss of INX-21 activity via RNA-mediated interference (RNAi)
does not result in any abnormalities, the precise role of INX-21 in C. elegans development and/or
behavior is not yet known; the INX-21 expression pattern has not been determined.
INneXin
INneXin
inx-5 encodes a predicted member of the innexin family; expressed in the embryonic hypodermis,
developing vulva, seam cells, and spermatheca.
inx-6 encodes an innexin, an integral transmembrane channel protein that is a structural component
of invertebrate gap junctions; INX-6 is required for formation of pharyngeal gap junctions and thus
for the electrical coupling and synchronous muscle contractions necessary for normal feeding
behavior and postembryonic development; INX-6 may function redundantly with EAT-5, another C.
elegans innexin; INX-6 expression is first detected in embryonic pharyngeal precursors and during
later larval and adult stages, in pharyngeal corpus muscles and isthmus marginal cells, where INX-6
localizes to plaque-like structures in the plasma membrane.
INneXin
inx-8 encodes a predicted member of the innexin family that affects fertility; expressed in sheath
cells.
ipp-5 encodes a type I inositol 5-phosphatase homolog; ipp-5 acts downstream of let-23 to
negatively regulate IP3 signaling and is involved in spermathecal contractions during ovulation; an
ipp-5::gfp transcriptional reporter is expressed in the adult distal spermatheca and weakly in the
proximal sheath.
isp-1 encodes a Rieske iron sulphur protein (ISP) which is a subunit of the mitochondrial complex
III in the mitochondrial membrane; the subunits are highly conserved in all mitochondria and
aerobic bacteria; mitochondrial complex III catalyses electron transport from ubiquinol to
cytochrome c; isp-1 mutants show low oxygen consumption, a decreased sensitivity to reactive
oxygen species and increased lifespan suggesting that mitochondrial electron transport is a key
factor affecting life span; isp-1 affects the rates of physiological processes like reproduction and
development and also affects behavior.
itr-1 encodes a putative inositol (1,4,5) trisphosphate receptor that affects the defecation cycle and
pharyngeal pumping, and also affects ovulation in a pathway downstream of LET-23; interacts with
UNC-54 in vivo, and is expressed in the adult intestine, pharynx, excretory cell, germ line, and
spermatheca, with limited neuronal expression.
jkk-1 encodes a member of the MAP kinase kinase superfamily that affects synaptic vesicle
localization and is required in type-D motor neurons for normal locomotion; can function in the
Hog1 MAP kinase pathway I in yeast as an activator of JNK and is expressed in most neurons
jnk-1 encodes a serine/threonine kinase that is the sole C. elegans member of the c-Jun N-terminal
kinase (JNK) subgroup of mitogen-activated protein (MAP) kinases; jnk-1 is required for normal
coordinated locomotion as well as for normal adult lifespan and response to heat and oxidative
stress; JNK-1 exhibits kinase activity in vitro that is dependent upon activation by the JKK1/MAPKK; in addition, JKK-1-dependent JNK-1 phosphorylation is required for JNK-1-mediated
lifespan extension, as is DAF-16, with which JNK-1 physically interacts and phosphorylates and
whose nuclear translocation is under JNK-1 control; a JNK-1::GFP translational fusion protein is
expressed in nearly all neuronal cell bodies and processes, including the nerve ring, head and tail
ganglions, and the dorsal and ventral nerve cords, at all stages of development.
lev-8 encodes a novel nicotinic acetylcholine receptor (nAChR) alpha subunit that is a member of
the ACR-8 group of nAChR subunits; LEV-8 activity is required for normal rates of pharyngeal
pumping and for fully wild-type responses (increased egg laying and body wall muscle contraction)
to the nAChR agonist and antihelmintic levamisole; expression of a LEV-8::GFP reporter construct
begins at the L1 larval stage and is detected in neurons, body wall and uterine muscle cells, and
socket cells of the IL and OL mechanosensory neurons; expression in body wall muscles is strongest
in the anterior, consistent with increased levamisole resistance of head, or anterior, muscles seen in
lev-8 mutant animals.
lim-6 encodes a LIM class homeodomain protein that contains two Zinc-finger-like LIM domains Nterminal to a predicted DNA-binding homeodomain; LIM-6 is predicted to function as a
lim-8
lim-8(ok941)
VC654
lim-9
lim-9(gk106)
VC209
lin-10
lin-10(e1439)
CB1439
lin-10(sy217)
PS906
lin-11
lin-11(sy251)
PS1174
lin-18
lin-18(e620)
CB620
lin-28
lin-28(n719)
MT1524
lip-1
lip-1(zh15)
AH102
transcription factor whose activity is required for regulating uterine morphogenesis and specific
aspects of terminal neuronal differentiation, including normal axonal morphology, full expression of
UNC-25/glutamic acid decarboxylase in select GABAergic neurons, and repression of sensory
receptor gene expression in the ASEL chemosensory neuron; LIM-6 is expressed in a group of nine
chemosensory-, inter-, and motorneurons, uterine toroid cells, spermathecal junction cells, and the
binucleate excretory gland cell.
lim-8 encodes proteins containing one PDZ and one LIM domain; in vitro binding and yeast twohybrid assays indicate that LIM-8 can physically interact with myosin heavy chain A (MYO-3) as
well as with UNC-96 and UNC-97, suggesting that LIM-8 is part of a structural component that
links membrane attachment proteins to myosin thick filaments; lim-8(RNAi) in a hypersensitive rrf3 background results in partially penetrant paralysis at mid-larval stages of development; a lim8::gfp promoter fusion is expressed in pharyngeal and body wall muscles, as well as in vulva,
spermathecae, anal sphincter and depressor muscles, head neurons, gonadal sheath, and the
excretory canal; staining with LIM-8 antibodies reveals that in body wall muscle LIM-8 localizes, at
least partially, to M-lines, around which myosin thick filaments are organized.
lim-9 encodes a protein containing one PET domain and six LIM domains and is orthologous to
Drosophila LIMPET and vertebrate FHL2; in vitro binding and yeast two-hybrid assays indicate that
LIM-9 physically interacts with UNC-96 and UNC-97 and thus, is likely a component of a protein
complex that links muscle focal adhesions to thick filaments; LIM-9 also enables Wnt-directed
planar cell polarity and is required for the fully asymmetrical division of B.a versus B.p cells, though
this requirement is quantitatively weak; a lim-9::gfp promoter fusion is expressed in pharyngeal and
body wall muscles, as well as in some neuronal processes, vulva, spermathecae, anal sphincter and
depressor muscles, gonadal sheath, and the excretory canal; staining with LIM-9 antibodies reveals
that in body wall muscle LIM-9 localizes, at least partially, to M-lines, around which myosin thick
filaments are organized.
lin-10 encodes a PDZ and PTB domain-containing protein that is homologous to mammalian Munc
interacting proteins (Mint1, OMIM:602414) and is required for polarized protein localization; LIN10 is required for proper localization of the LET-23 EGF receptor to the basolateral membrane of
the vulval precursor cells and for proper postsynaptic localization of GLR-1, an AMPA-type
glutamate receptor in interneurons; LIN-10 is detected in the cytoplasm, membrane, and at
particularly high levels in the Golgi.
lin-11 encodes a predicted LIM homeodomain transcription factor that affects vulval development,
neuronal development and fate specification, utse cell differentiation, and fertility; it is expressed in
some neurons, the vulva, pi cells and their progeny, and the spermatheca.
lin-18 encodes a predicted receptor tyrosine kinase that is a member of the Ryk/Derailed family of
tyrosine kinase-related receptors (OMIM:600524, mutations in humans are associated with cleft
palate); in C. elegans, LIN-18 is required for establishing the polarity of the secondary vulval cell
lineage produced by the P7.p vulval precursor cell; LIN-18 may be a receptor for Wnt-like signaling
molecules, and in vulval development appears to function independently of, but in parallel with,
LIN-17, a Frizzled-like Wnt receptor, also required for proper orientation of the P7.p lineage; a lin18 reporter gene is expressed in body wall muscle, neurons, and the developing vulva; in the vulva,
expression is detected in P5.p, P6.p, and P7.p and all of their descendants during the L3 and L4
larval stages.
lin-28 encodes a cytoplasmic protein with a cold shock domain and retroviral-type (CCHC) zinc
finger motifs; LIN-28 is required for events specific to the second larval stage, which in lin-28
mutants are skipped, and is itself subject both to negative regulation (by binding of the lin-4 stRNA
to an element in the lin-28 3' UTR) and to positive regulation (by LIN-14, which negatively
regulates lin-4-independent inhibition also acting on the lin-28 3' UTR).
lip-1 encodes a mitogen-activated protein (MAP) kinase phosphatase homologous to the vertebrate
dual specificity phosphatase MKP-3; during development, LIP-1 negatively regulates MAP kinase
activity to control the extent of germline proliferation and oocyte meiotic cell cycle progression; lip1 activity is also required redundantly with dep-1 to negatively regulate MAPK signaling during
vulval induction; in addition, lip-1 is required for normal embryonic development; lip-1 expression
begins during embryogenesis and continues through adulthood; expression is seen in most somatic
cells and in germ cells of the pachytene region, transition zone and proximal-most region of the
mitotic zone; in the pachytene region, LIP-1 is associated with the plasma membrane; in early L3
larvae, LIP-1 expression increases in secondary vulval precursor cells in a lin-12/Notch-dependent
manner, suggesting that lip-1 may be a direct downstream target of lin-12-mediated signaling;
interaction with the Notch pathway is further demonstrated by chromatin immunoprecipitation
experiments showing that, in the germline, the lip-1 promoter region coprecipitates with LAG-3;
mec-12
mec-12(e1605)
CB3284
mec-2
mec-2(e75)
CB75
mek-1(ks54)
FK171
mig-10(ct41)
BW315
mek-1
mig-10
mkk-4
mkk-4(ok1545)
VC1089
nhr-83
nhr-83(ok1613)
RB1416
nlp-1(ok1469)
RB1340
nlp-1(ok1470)
RB1341
nlp-1
nlp-12
nlp-12(ok335)
RB607
nlp-15
nlp-15(ok1512)
VC1063
nlp-17(ok3461)
RB2498
nlp-18(ok1557)
RB1372
nlp-17
nlp-18
nlp-20
nlp-3
nlp-5
nlp-8
nlp-20(ok1591)
RB1396
nlp-3(ok2688)
RB2030
nlp-5(ok1981)
RB1609
nlp-8(ok1799)
VC1309
germline lip-1 mRNA accumulation is negatively regulated by the FBF proteins (FBF-1 and FBF-2)
that bind to the lip-1 3'UTR.
mec-12 encodes an alpha-tubulin; MEC-12 is required for normal mechanosensory response to
gentle touch, and specifically for formation of the 15-protofilament microtubule bundle present in
the touch receptor neurons; mec-12 interacts genetically with mec-5, which encodes a unique C.
elegans collagen secreted by the hypodermis; MEC-12 is highly expressed in the touch neurons as
well as in several other neurons that do not contains the microfilament bundle, such as the ventral
cord motorneurons; MEC-12 is acetylated in a manner that is dependent upon MEC-17 and
W06B11.1, which encode paralogous alpha-tubulin acetyltransferases.
The mec-2 gene encodes a stomatin homolog required to sense gentle mechanical stimuli (e.g.
touch) along the body wall.
mek-1 encodes a MAP kinase kinase (MAPKK) that is involved in the stress response to heavy
metals and starvation, and that has the highest homology to mammalian MKK7.
mig-10 encodes proteins that contain, from N- to C-terminus, an RA-like (Ras association) domain,
a PH (pleckstrin homology) domain, and a proline-rich motif, and that are homologous to the
vertebrate RIAM, lamellopodin, and Grb7, Grb10, and Grb14 cytoplasmic adaptor proteins; during
development, mig-10 activity is required for cell migration and axon outgrowth; in regulating axon
outgrowth, mig-10 likely functions downstream of unc-6/Netrin and slt-1/Slit and in concert with
UNC-34, with which it interacts in vitro; mig-10::gfp reporter fusions are expressed in neurons as
well as in pharyngeal and intestinal tissue; when expressed in tissue culture cells, a MIG-10::GFP
fusion protein colocalizes with F-actin and promotes lamellipodia formation.
mkk-4 encodes a MAP (mitogen-activated protein) kinase kinase that is a member of the MKK4
family of MAPKK's; MKK-4 activity is required in presynaptic neurons, in a dose-dependent
manner, for normal presynaptic development and morphology; in regulating presynaptic
organization, MKK-4 acts upstream of PMK-3/MAPK and downstream of DLK-1/MAPKKK,
whose levels are negatively regulated by the RPM-1 ubiquitin ligase; a functional MKK-4::GFP
fusion protein is expressed in the cytoplasm of many neurons as well as in other cell types, including
the pharyngeal muscles.
Nuclear Hormone Receptor family
nlp-1 encodes a predicted neuropeptide-like protein of the MSFamide family with similarity to
Aplysia californica (sea hare) buccalin, a neuropeptide that regulates acetylcholine-induced muscle
contraction; NLP-1 is expressed in the phasmid PHB tail sensory neuron, lateral neurons, head
neurons, and the intestine; the precise role of NLP-1 in nervous system function and development is
not yet known.
nlp-12 encodes two predicted neuropeptide-like proteins; nlp-12 is part of a LQFamide neuropeptide
family that has members in at least one other nematode species; nlp-12 is expressed in one tail
neuron; as loss of nlp-12 activity via large-scale RNAi screens does not result in any obvious
abnormalities, the precise role of nlp-12-encoded peptides in development and/or behavior is not yet
known.
Neuropeptide-Like Protein
Neuropeptide-Like Protein
nlp-18 encodes four predicted neuropeptide-like proteins; in C. elegans, nlp-18 is part of the FAFA
neuropeptide family that also contains nlp-20; nlp-18 is expressed in a variety of neurons, including
ASI, NSM, four head neurons, two tail neurons, and two anterior pharyngeal neurons; nlp-18
expression is also detected in the spermatheca, the rectal gland, and the intestine; as loss of nlp-18
activity via large-scale RNAi screens does not result in any obvious abnormalities, the precise role
of nlp-18-encoded peptides in development and/or behavior is not yet known.
nlp-20 encodes a predicted neuropeptide of the FAFA family; expressed in pharyngeal neurons.
nlp-3 encodes a neuropeptide-like protein of the GFxGF family with similarity to orcokinins, highly
conserved peptides native to crustaceans that enhance hindgut contractions; NLP-3 is expressed in
neurons in the head, pharynx, and vulva, and in the intestine; the precise role of NLP-3 in nervous
system function and development is not yet clear.
Neuropeptide-Like Protein
Neuropeptide-Like Protein
nsy-1
nsy-1(ok593)
VC390
octr-1
octr-1(ok371)
VC224
odr-3
odr-3(n2150)
CX2205
pde-1
pde-1(gk891)
VC1856
pde-1(gk906)
VC1844
pes-7(gk123)
VC145
pes-7
plc-1
plc-1(rx1)
PS4112
plc-2
plc-2(ok1761)
RB1496
plc-3
plc-3(tm1340)
PS4886
plc-4
plc-4(ok1215)
RB1173
pld-1(ok2222)
RB1737
pld-1
plx-1
plx-1(nc36)
ST36
ptb-1
ptb-1(gk113)
VC119
R13H7.2(ok1167)
RB1141
R13H7.
2
nsy-1 encodes a MAP kinase kinase kinase (MAP3K) that is orthologous to the mammalian
apoptosis signal-regulating kinase (ASK) family of protein kinases; nsy-1 activity is required for
chemotaxis, egg laying, pathogen response, and response to anoxia; NSY-1 activity is activated by
the calmodulin kinase UNC-43, and is required for lateral signalling that leads to asymmetric
olfactory neuron fates; NSY-1 interacts with SEK-1, and is expressed in the intestine, hypodermis,
rectal gland cells, and neurons.
octr-1 encodes a predicted G-protein-coupled seven-transmembrane domain biogenic amine
receptor; an OCTR-1::GFP fusion protein is expressed in a very restricted pattern nearly exclusively
in a subset of head and tail neurons.
odr-3 encodes a G protein alpha subunit; odr-3 activity is required for normal chemotaxis, odorant
avoidance, and nociceptive function as well as cilium morphogenesis in chemosensory neurons; an
ODR-3::GFP is expressed in five pairs of sensory neurons AWA, AWB, AWC, ASH, and ADF; the
AWC neurons consistently express GFP most strongly, while the AWB neurons express at lower
levels and the AWA, ASH, and ADF neurons express only weakly; in AWC neurons, ODR-3::GFP
localizes to cilia which have a characteristic wing-shaped morphology.
pde-1 encodes one of six C. elegans cyclic nucleotide phosphodiesterases; PDE-1 is most closely
related to the calcium/calmodulin (CaM)-dependent phosphodiesterases and binds bovine
calmodulin in vitro in a calcium-dependent manner.
pes-7 encodes an IQGAP ortholog; IQGAP proteins bind actin and CLIP-170, effect activities of the
Rho family GTPases Rac1 and Cdc42, and function in cytokinesis; PES-7 is required for completing
meiosis and mitosis, and for germline formation and maintenance; IQGAP's alpha-actinin domain is
related distantly to alpha-actinin domains in calponin, transgelin (SM22 alpha), and the protooncogene Vav; a pes-7 reporter is first expressed in the ventral nerve cord of the elongating embryo
and in later stages of development is also expressed in all major ganglia, the vulva, and in the
spermathecal valves; in the ventral nerve cord, pes-7 expression is detected in nuclei as well as in
cell bodies and neural processes.
plc-1 encodes a predicted phospholipase C that affects fertility and possesses two functional
domains not commonly seen in other phospholipases: a C-terminal Ras-associating domain with
structural similarity to RalGDS and AF-6, and an N-terminal CDC25-like domain that possesses
structural homology to guanine nucleotide exchange proteins for Ras.
plc-2 encodes one of five C. elegans phospholipase C (PLC) isozymes; the amino acid sequence of
PLC-2 is most closely related to members of the PLC-beta group, but is divergent and does not
include an extended C terminus typical of other PLC-betas.
plc-3 encodes a phospholipase C gamma homolog; PLC-3 activity is required for regulation of a
number of biological processes, including ovulatory sheath contractions, nose touch, behavioral
quiescence, oscillatory Ca2+ signaling in the intestine, and innate immunity; plc-3 reporter fusions
are expressed in sheath cells and the spermatheca, the intestine, embryonic cells including the
epidermal cells during morphogenesis, and the ALA neuron.
PhosphoLipase C
pld-1 encodes the C. elegans ortholog of phospholipase D; by homology, PLD-1 is predicted to
hydrolyze phosphatidylcholine (PC) to phosphatidic acid (PA) and choline; loss of pld-1 activity via
RNAi reveals that pld-1 may play a role in phagosome maturation; large-scale expression studies
indicate that pld-1 is widely expressed in larvae and adults, and seen in the pharynx, intestine,
nervous system, body wall muscle, and hypodermis.
plx-1 encodes a C. elegans plexin ortholog; by homology, PLX-1 is predicted to function as a
semaphorin receptor whose activity is required for proper positioning of the ray 1 cells in the male
tail; genetic analyses indicate that while plx-1 functions in the same genetic pathway as the smp-1
and smp-2 semaphorin-encoding genes to position ray 1 cells, it functions in parallel to unc-73/GEF
and the ced-10, mig-2, and rho-1 GTPase genes in affecting ray 1 position; plx-1 reporter gene
fusions are expressed in all body wall muscles, male sex-specific muscles, and lateral hypodermal
cells during postembryonic development; in the male tail, during the L3 larval stage when ray 1 cells
are positioned, the plx-1 reporter is expressed predominantly in cells of the ray 1 and ray 2 lineages,
with weaker and transient expression visible in the more posterior 3-9 rays.
human PTB (hnRNP) homolog
R13H7.2 gene
rab-3
rab-3(js49)
NM791
rab-6.2
rab-6.2(ok2254)
VC2117
rap-1
rap-1(pk2082)
TZ181
rap-2
rap-2(gk11)
VC14
rgl-1
rgl-1(ok1921)
RB1576
rgs-3(vs19)
LX242
rgs-3
ric-3
ric-3(hm9)
MF200
ric-4
ric-4(gk312)
VC709
rop-1
rop-1(pk93)
MQ470
rpm-1
rpm-1(ok364)
RB630
rab-3 encodes a rab3 homolog, a member of the Ras GTPase superfamily, and affects sensitivity to
aldicarb and the distribution of synaptic vesicle populations and thereby affects synaptic
transmission, track amplitude and speed of movement, chemotaxis to isoamyl alcohol, affects
pharyngeal pump durations, and may only slightly affect male mating behavior; requires aex-3 for
localization to synapse-rich regions in axons and it is expressed in most or all neurons.
rab-6.2 encodes a small, monomeric Rab GTPase that is most closely related to the Drosophila and
mammalian Rab6 GTPases; by homology, RAB-6.2 is predicted to function in the regulation of
intracellular membrane trafficking; RNAi experiments indicate that rab-6.2 is required redundantly
with rab-6.1 for normal embryonic development and reproduction.
rap-1 encodes a member of the Ras superfamily of small GTPases; the activated protein interacts
with W05B10.4 and T14G10.2 in yeast two-hybrid assays and rap-1 is expressed in some neurons in
the head and tail, the rectal epithelial cells, body muscle, hypodermis, and in the somatic cells of the
gonad.
rap-2 encodes a Ras-related GTPase that is most similar to the RAP2 members of the Ras GTPase
superfamily; by homology, RAP-2 is predicted to function as a membrane-localized GTPase that
likely plays a role in signal transduction; as animals homozygous for a rap-2 deletion mutation show
no obvious abnormalities, the precise role of RAP-2 in C. elegans development and/or behavior is
not yet known.
Ral GDS-Like
rgs-3 encodes three proteins containing two RGS (regulator of G protein signaling) domains, the
more C-terminal of which is most similar to those of the mammalian brain-specific RGS, RGS8;
rgs-3 activity is required for normal G protein-mediated response to a number of sensory stimuli,
including odorants, high osmolarity, and nose touch off food; genetic analyses indicate that RGS-3
functions to decrease G protein signaling in sensory neurons and increase glutamatergic synaptic
transmission from sensory to interneurons; RGS-3::GFP fusion proteins are expressed exclusively in
nine pairs of sensory neurons from late stages of embryogenesis through adulthood.
ric-3 encodes a novel, highly charged protein with two transmembrane domains and extensive
coiled-coil domains; RIC-3 is necessary for the maturation and function of at least four nicotinic
acetylcholine receptors; specifically, it is needed for assembly or trafficking of the DEG-3 nicotinic
acetylcholine receptor; RIC-3 levels and hence, activity, are regulated by BATH-42, a BTB and
MATH domain-containing protein, with which RIC-3 interacts in vitro; as BATH-42 also interacts
with the CUL-3 cullin, RIC-3 levels are thus likely regulated by a CUL-3-containing ubiquitin ligase
complex.
ric-4 encodes an ortholog of vertebrate SNAP-25 and S. cerevisiae Sec9p; SNAP-25 is associated
with synaptosomes, required for axonal growth in vivo, and targeted by botulinum neurotoxins;
UNC-86 and MEC-3 are required for ric-4 expression, and act on a regulatory element (I2h) in ric-4
conserved between the first introns of C. elegans and C. briggsae ric-4 genes; other conserved motifs
in the promoter region (P1 and P2) and first intron (I1h, I1m, I2h, and I2m) are required for ric-4
expression in DA and DD motor neurons (P1), DB and DA neurons (I1m and I2m), amphid and
phasmid neurons (P2), pharyngeal neurons (I1h), and mechanosensory neurons (I2h); loss of ric-4
function via RNAi results in aldicarb resistance, indicating that ric-4 plays a role in synapse
structure and function.
rop-1 encodes an RNAi-binding protein that is orthologous to the vertebrate 60-kDa Ro autoantigen
that is the protein component of the Ro ribonucleoprotein (RNP) complex; ROP-1 binds the single
C. elegans Ro RNP RNA component, YRN-1 (Y RNA) in vivo and although loss of rop-1 activity
via mutation results in no obvious visible phenotypes, it does result in a dramatic decrease in YRN-1
levels, indicating that ROP-1 is necessary for maintaining normal levels of the Ro RNP Y RNA; in
addition, rop-1 mutations also result in a statistically significant increase in mutant 5S rRNA
molecules found in ribosomal RNA preparations, suggesting that ROP-1 may play a role in quality
control of 5S rRNA processing; rop-1 mRNA is detectable during all stages of development, and
rop-1 promoter fusions appear to be expressed in all cell types, except the germline.
rpm-1 encodes an E3 ubiquitin ligase that contains an N-terminal RCC1 (regulator of chromosome
condensation)-like guanine nucleotide exchange factor (GEF) domain and that is orthologous to
Drosophila highwire and murine Phr1; RPM-1 functions autonomously within several different
types of neurons to regulate presynaptic differentiation; in regulating axon termination, RPM-1 acts
through the GLO-4 guanine nucleotide exchange factor that positively regulates vesicular trafficking
through GLO-1/Rab; in regulating synaptogenesis, RPM-1 functions as part of an SCF-like ubiquitin
ligase complex that negatively regulates signaling through the DLK-1 MAP kinase cascade; RPM-1
is expressed in most, if not all, neurons from the comma stage of embryogenesis through adulthood;
rpy-1
rpy-1(ok145)
NM1581
sax-3
sax-3(ky123)
CX3198
sbt-1
sbt-1(ok901)
RB987
scrm-1
scrm-1(tm698)
CU2904
sek-1
sek-1(km4)
KU4
sem-5(cs15)
UP148
sem-5
ser-7
ser-7(tm1325)
DA2100
sir-2.1
sir-2.1(ok434)
VC199
slo-1
slo-1(js118)
NM1630
snb-1
snb-1(md247)
NM467
snb-1(js44)
NM833
RPM-1 expression is also seen in the pharynx, coelomocytes, and distal tip cells; in neurons, RPM-1
localizes to presynaptic terminals.
rpy-1 is orthologous to the human gene 43KDA ACETYLCHOLINE RECEPTOR-ASSOCIATED
PROTEIN (RAPSN; OMIM:601592), which when mutated leads to congenital myasthenic
syndrome.
sax-3 encodes, by alternative splicing, two isoforms of an ortholog of Drosophila ROUNDABOUT,
ROBO3, and LEAK, and of human ROBO1, ROBO2 (OMIM:602431, mutated in vesicoureteral
reflux), and ROBO3 (OMIM:608630, mutated in horizontal gaze palsy with progressive scoliosis);
in larval hermaphrodites, SAX-3 is required to confine migrating sex myoblasts to the ventral
muscle quadrants during their migration through the body and for multiple aspects of sensory,
motor, and interneuron axon guidance.
sbt-1 encodes the C. elegans ortholog of the neuroendocrine chaperone 7B2; by homology, SBT-1 is
predicted to function in the maturation/activation of the EGL-3/PC2 proprotein convertase;
accordingly, mass spectrometry analysis indicates that sbt-1 activity is required for production of
some neuropeptides; sbt-1 mutant animals are also aldicarb resistant, suggesting that SBT-1 is
required for normal cholinergic signaling; in both in vitro and in vivo assays, SBT-1 facilitates
maturation of vertebrate proPC2; sbt-1 promoter fusions are expressed in most neurons and in the
pharynx; when expressed in DA cholinergic neurons under the control of the unc-129 promoter,
SBT-1::YFP localizes to puncta adjacent to the synaptic vesicle reporter SNB-1::RFP.
scrm-1 encodes, by alternative splicing, two isoforms of a putative phospholipid scramblase required
for phosphatidylserine exposure and the normally rapid engulfment of apoptotic cells in the
germline; SCRM-1 is localized to plasma membranes of embryonic cells from early embryogenesis
onward; SCRM-1 is specifically bound by residues 380-550 of WAH-1 in vitro, and WAH-1
binding is required in liposomes for more than residual SCRM-1 activity; in scrm-1(tm698) or scrm1(tm805) embryos, apoptotic cells do eventually disappear, but their removal is delayed; SCRM-1 is
homologous to human PLSCR1-5, and paralogous to SCRM-2 through SCRM-8.
SEK-1 has MAPKK activity and belongs to the MAPKK family; SEK-1 can activate both JNK-1
and PMK-1 in the yeast Hog pathway.
sem-5 encodes a Src homology (SH) domain 2 and 3-containing protein, orthologous to human
GRB2 (OMIM:108355) and Drosophila Drk; sem-5 functions in multiple signaling pathways during
development including those regulating sex myoblast migration, muscle membrane extension, vulval
induction, fluid balance, viability, and formation of the male tail; SEM-5 acts downstream of the
LET-23 epidermal growth factor receptor to negatively regulate RAS-, MAP-, and IP-3-, mediated
signal transduction; a sem-5::yfp promoter fusion is expressed in many cells throughout
development, including the hypodermis, intestine, neurons, body wall muscles, and vulval precursor
cells.
ser-7 encodes an ortholog of mammalian 5-HT7 metabotropic serotonin receptors; SER-7 is required
for stimulation of egg-laying or pharyngeal pumping by serotonin (5-HT), for regular pumping in
response to bacteria, and probably also for 5-HT to activate MC neurons; SER-7 and SER-1 are
redundantly required for normal egg-laying; SER-7 is expressed in head and tail neurons,
pharyngeal neurons (M4, MCs, I2s, I3, M5, M3s, I4, I6, and M2s), vulval muscles, and intestine;
heterologously expressed SER-7, when challenged with 5-HT, stimulates intracellular adenylate
cyclase activity; SER-7 has high affinity for 5-HT and tryptamine, but not for 5-CT, and is
unaffected by at least some agonists of mammalian 5-HT7 receptors.
sir-2.1 encodes one of four C. elegans proteins with similarity to the Saccharomyces cerevisiae Sir2p
NAD-dependent histone deacetylase; increasing the dosage of sir-2.1 by a chromosomal duplication
extends lifespan by up to 50%, which parallels the life extension of yeast by increased SIR2 dosage;
genetically, a sir-2.1 transgene functions upstream of daf-16 in its effects on lifespan.
slo-1 encodes a voltage- and calcium-activated potassium (BK) channel; SLO-1 activity is required
for muscle inactivation: mutants have wild-type levels of motor activity, but have less smooth
movement and tend to stop and reverse direction; SLO-1 is expressed in neurons and in body wall
and vulval muscle; SLO-1 localization in proximity to the EGL-19 L-type calcium channel in
muscle membrane is mediated by the dystrophin-associated protein complex (DAPC) and the ISLO1 adapter protein with which SLO-1 physically interacts and also colocalizes with in muscle
membrane.
The snb-1 gene encodes synaptobrevin, a synaptic vesicle protein orthologous to human vesicleassociated membrane protein 1 (VAMP1 OMIM:185880) and 2 (VAMP2 OMIM:185881), and is
required for viability and synaptic transmission; SNB-1 is likely to play a role in vesicle docking
and/or fusion and is expressed in neurons where it colocalizes with synaptic vesicle proteins RAB-3
and synaptotagmin.
sng-1
sng-1(ok234)
RB503
snt-1
snt-1(ad596)
DA596
soc-2
soc-2(ku167)
MH1019
sta-1
sta-1(ok587)
RB796
stdh-1
stdh-1(ok569)
RB786
sulp-1
sulp-1(ok1639)
RB1436
sur-6
sur-6(ku123)
MH1292
syd-1
syd-1(ju82)
CZ1893
syd-2
syd-2(ok217)
ZM607
syd-2(ju37)
CZ900
sng-1 encodes the C. elegans synaptogyrin ortholog, a vertebrate integral membrane synaptic vesicle
protein; loss-of-function mutations in sng-1 result in no obvious defects in synaptogenesis or
neuronal activity, suggesting that SNG-1 is likely required for more subtle neuronal functions; SNG1::GFP reporters are expressed throughout the nervous system in neurons in the dorsal and ventral
nerve cords, as well as the anterior nerve ring; SNG-1 colocalizes with the synaptic vesicle
component SNT-1.
snt-1 encodes two proteins, SNT-1A and SNT-1B, that are orthologous to the synaptic vesicle
protein synaptotagmin 1; snt-1 is required for synaptic vesicle recycling (endocytosis) as well as for
proper control of synaptic vesicle exocytosis and neurotransmitter release; accordingly, snt-1
activity is required for a variety of behaviors including pharyngeal pumping, locomotion, and
defecation; SNT-1A and SNT-1B isoforms are expressed in neurons, with SNT-1A typically
expressed at higher levels, and in a greater number of neurons, than SNT-1B; in addition, SNT-1B is
exclusively expressed in the excretory duct cell and a group of tail neurons including DVB, a
GABAergic neuron required for defecation.
soc-2 encodes a leucine-rich repeat protein; soc-2 functions downstream in the let-60/Ras and egl15/FGF receptor signaling pathways to positively and negatively regulate signaling through these
pathways, respectively, and thus affect such processes as vulval development, osmoregulation, and
muscle membrane extension; consistent with its role in regulating Ras-mediated signal transduction,
SOC-2 interacts with LET-60/Ras in yeast two-hybrid assays; soc-2 is reported to be widely
expressed in larval and adult tissues.
sta-1 encodes a protein that is a member of the STAT family of transcription factors; from N- to Cterminus, STA-1 contains conserved coiled-coil, DNA-binding, and SH2 domains, but apparently
lacks a conserved amino-terminal oligomerization domain found in other STAT family members;
sta-1 activity is required for repressing dauer formation at high temperatures and genetic analyses
indicate that STA-1 acts redundantly with some members of the DAF-7/TGF-beta signaling pathway
to repress dauer formation, particularly at low temperatures; tyrosine-phosphorylated STA-1 is able
to bind a high affinity mammalian STAT binding sequence, and the STA-1 C-terminus can function
as a transcriptional activation domain; sta-1 is widely expressed during most life stages, including
the dauer stage, and is found in the pharynx, intestine, body wall muscles, and in neurons; STA-1
localizes to both the cytoplasm and the nucleus, with expression in the latter found particularly in
some amphid neurons; in some neurons, STA-1 expression appears to be negatively regulated by
DAF-7/TGF-beta signaling.
stdh-1 encodes a putative steroid dehydrogenase required for normally short lifespan; STDH-1 is
orthologous to human HSD17B3 (OMIM:605573, mutated in pseudohermaphroditism), HSD17B12
(OMIM:609574), and HSDL1, and paralogous to LET-767 and STDH-2/-4; STDH-1 is expressed in
larval intestine, and in both larval and adult body wall muscle and neurons.
sulp-1 encodes one of eight C. elegans members of the sulfate permease family of anion
transporters; by homology, SULP-1 is predicted to function as an anion transporter that regulates
cellular pH and volume via transmembrane movement of electrolytes and fluids; a sulp-1::GFP
transcriptional fusion is expressed strongly in several neurons, weakly in hypodermal cells and the
intestine, and very faintly in the excretory cell and body wall muscle.
sur-6 encodes a regulatory (B) subunit of serine/threonine protein phosphatase 2A (PP2A-B); sur-6
was initially identified in screens for mutations that suppress the Multivulva phenotype produced by
an activated let-60/Ras mutation and enhance the vulvaless and larval lethality phenotype of a
hypomorphic lin-45/Raf mutation; in addition, RNAi experiments demonstrate that sur-6 activity is
also essential for embryonic development; genetic studies indicate that during vulval development
SUR-6 likely acts with the KSR-1 kinase in a parallel pathway that positively regulates RTK-RasMAP kinase signaling.
syd-1 encodes a protein that contains a Rho-GTPase-like activating domain as well as PDZ and C2
domains; during neuronal development, SYD-1 is required cell autonomously to positively regulate
synaptogenesis; in regulating synapse development, SYD-1 functions as a positive regulator of
SYD-2/liprin through direct interaction with ELKS-1, a pre-synaptic protein also required for
synapse development; in turn, SYD-1 activity is regulated by RSY-1, a negative regulator of
synaptogenesis, with which it also interacts physically; SYD-1 is expressed in neurons and localizes
to presynaptic regions.
syd-2 encodes alpha-liprin, a member of the liprin family of proteins that interact with LAR
(leukocyte common antigen related)-type receptor tyrosine phosphatases (RPTPs) to facilitate
clustering of RPTPs to focal adhesions; SYD-2 is required for establishing normal presynaptic
density, and is expressed in all neurons and muscles; SYD-2 is required cell autonomously in
neurons for differentiation of presynaptic active zones, where SYD-2 is localized.
T02E9.3
T02E9.3(ok568)
RB785
T10B11
.2
tag-49
T10B11.2(ok1252
) RB1203
tag-49(ok381)
VC270
tax-2(p691)
PR691
tax-2
tax-6
tax-6(p675)
PR675
tbx-8
tbx-8(ok656)
RB831
tpa-1(k530)
MJ563
tpa-1
trp-1
trp-1(sy690)
PS4323
twk-18
twk-18(cn110)
TN110
tyra-3
tyra-3(ok325)
VC125
unc-103
unc-103(e1597)
CB1597
unc-104
unc-104(e1265)
CB1265
unc-108
unc-108(n501)
MT1093
T02E9.3/dop-5 encodes a homolog of human melatonin type 1b receptors, and more generally of
mammalian dopamine and serotonin (5-HT) receptors; dop-5 is partly required for male tail curling,
with dop-5 (RNAi) animals showing reduced curling in exogenous 5-HT; dop-5 is required for full
sensitivity to 5-HT, normal brood sizes, and pharyngeal pumping; dop-5 is expressed in head and
tail neurons.
T10B11.2 gene
Temporarily Assigned Gene name
tax-2 encodes a cyclic nucleotide-gated channel beta subunit orthologous to the human gene ROD
PHOTORECEPTOR CNG-CHANNEL BETA SUBUNIT (CNGB1; OMIM:600724), which when
mutated leads to disease; TAX-2 activity is required for chemosensation, thermosensation,
regulation of dauer larval development, normal axon guidance for some sensory neurons, and
regulation of axonal outgrowth and morphology in late larval stages; a tax-2::GFP promoter fusion
is expressed in nine pairs of amphid sensory neurons and a TAX-2::GFP fusion protein localizes to
developing axons and sensory cilia.
tax-6 encodes an ortholog of calcineurin A that is required for inhibition and adaptation of several
sensory neurons and for the normal regulation of egg-laying by serotonin; TAX-6 stimulates
transcription of rcn-1, and binds RCN-1 protein if free Ca[2+] is present; in general, calcineurin
positively regulates calcium-dependent signaling; tax-6 loss-of-function mutants exhibit an extended
lifespan which is characterized by enhanced autophagy and dependent upon the presence of
functional bec-1.
T BoX family
tpa-1 encodes two protein kinase C isoforms, TPA-1A and TPA-1B; analysis of tpa-1 mutations
indicates that at least one TPA-1 isoform plays a role in nicotine-induced adaptation and that both
isoforms appear to play a role in gpa-12/G protein-mediated signaling that modulates feeding and
growth.
trp-1 encodes a transient receptor potential (TRP) channel that, along with TRP-2 and SPE-41,
constitutes the three C. elegans members of the TRPC subfamily; trp-1, along with trp-2, control
nicotine-dependent behavior; a TRP-1::GFP reporter fusion is expressed in motor neurons,
interneurons, vulval and intestinal muscles, and the BAG sensory neuron.
twk-18 encodes one of 44 C. elegans TWK (two-P domain K+) potassium channel subunits that
contain two pore-forming domains and four transmembrane domains; TWK-18 was originally
defined by gain-of-function mutations that result in embryonic lethality at the two-fold stage,
locomotion defects, longer than normal body length, abnormal egg-laying, and temperature-sensitive
paralysis; as loss of TWK-18 function via reversion or RNA-mediated interference does not result in
any abnormalities, TWK-18 likely functions redundantly with other TWK channels; TWK-18 can
function as an outwardly rectifying K+ channel, and is activated by temperature increases, thus
making it a temperature-gated channel; TWK-18 is expressed in body wall muscle.
tyra-3 encodes a homolog of octopamine or tyramine receptors that is expressed in head neurons
(anterior deirid and cephalic sensilla), tail neurons, and vulva; TYRA-3 is required for normal
inhibition of movement by 5-HT, with tyra-3(RNAi) animals being hyperactive; heterologously
expressed TYRA-3 has no effect on adenylate cyclase activity.
unc-103 encodes an ether-a-go-go-related (ERG) K+ channel homolog, orthologous to human
KCNH6 (OMIM:608168); UNC-103 regulates muscle activation in motility, egg-laying and male
spicule protraction; UNC-103 is expressed highly in many neurons; gain-of-function unc-103 alleles
can be uncoordinated, while loss-of-function alleles have a more subtle defect in copulatory spicule
protraction.
unc-104 encodes a kinesin-like motor protein homologous to human axonal transporter of synaptic
vesicles (ATSV, OMIM: 601255); UNC-104 is required for anterograde axonal transport of synaptic
vesicles as well as differentiation of pre- and postsynaptic domains at inhibitory neuromuscular
junctions; UNC-104 is expressed solely in neurons; UNC-104 retrograde movement is regulated by
PTL-1/Tau, with which it physically interacts in vivo.
unc-108 encodes a small GTPase homologous to the Rab GTPases that function in endocytosis,
membrane fusion, and vesicular trafficking events; unc-108 function is required in neurons for
normal locomotion; unc-108 also functions in the removal of apoptotic cells, specifically it functions
in engulfing cells for the recruitment and fusion of the lysosome to the phagosome; unc-108 is
expressed in neurons and in engulfing cells.
unc-13
unc-13(e1091)
CB1091
unc-2
unc-2(e55) CB55
unc-25
unc-25(e156)
CB156
unc-26
unc-26(e205)
CB205
unc-31
unc-31(e169)
CB169
unc-37
unc-37(e262)
CB262
unc-44
unc-44(e362)
CB362
unc-49(e407)
CB407
unc-49
unc-54
unc-54(e190)
CB190
unc-58
unc58(e665e2112)
CB2842
unc-13 encodes at least five protein isoforms that regulate neurotransmitter release by altering the
conformation of syntaxin; UNC-13 proteins are required for normal pharyngeal pumping and
thrashing in liquid, normally short lifespan, normally large brood sizes, and full adult body sizes;
UNC-13 proteins have orthologs in vertebrates and Drosophila; UNC-13 proteins are complex, with
multiple C2, phorbol ester-binding, and DUF1041 domains; UNC-13 protein form is localized to
most or all synapses; many of the unc-13 mutant alleles with viable phenotypes are transcriptspecific, while homozygotes with an unc-13 null (deletion) allele die as paralyzed first-stage larvae.
unc-2 encodes a calcium channel alpha subunit required for desensitization to dopamine, normal
flexion and speed during movement, normally low sensitivity of whole animals to serotonin, and
neuronal migrations promoted by humoral serotonin; UNC-2 is orthologous to human CACNA1A
(OMIM:601011, mutated in familiar hemiplegic migraine or episodic ataxia 2) and to Drosophila
CACOPHONY; UNC-2 is expressed primarily in motor neurons, several sensory neurons, and HSN
and VC neurons controlling egg-laying.
unc-25 encodes the C. elegans ortholog of the GABA neurotransmitter biosynthetic enzyme,
glutamic acid decarboxylase (GAD); unc-25 activity is required for GABA synthesis and thus for
normal synaptic transmission and GABA-mediated behaviors; UNC-25 is expressed specifically in
the 26 GABAergic neurons as soon as they are generated and localizes to cell bodies, axonal
branches, and synaptic regions, including some localization to synaptic vesicles; in the 19 type D
GABAergic neurons, unc-25 expression is positively regulated by the UNC-30 homeodomain
transcription factor, which binds to the unc-25 promoter in a sequence-specific manner.
unc-26 encodes synaptojanin, a polyphosphoinositide phosphatase orthologous to human
synaptojanin 1 (OMIM:604297, 309000, which when mutated leads to Lowe oculocerebrorenal
syndrome); UNC-26 is required for normal locomotion, pharyngeal pumping, and defecation, and
specifically, appears to function in multiple steps of synaptic vesicle recycling; UNC-26 may also
play a role in cytoskeletal organization.
unc-31 encodes a pleckstrin homology (PH) domain-containing protein that is the C. elegans
ortholog of human CADPS/CAPS (calcium-dependent activator protein for secretion
OMIM:604667); UNC-31 functions in post-docking calcium-regulated dense-core vesicle fusion
that is required for egg laying, locomotion, pharyngeal pumping, and recovery from the dauer larval
stage; in addition, UNC-31 functions in the insulin receptor signaling pathway that regulates adult
life span where it may control Ca[2+]-regulated secretion of an insulin-like ligand; UNC-31 is not
required for synaptic vesicle exocytosis; unc-31::gfp transcriptional reporters are expressed in most,
if not all, neurons, vulval muscles, vulval cells, the spermatheca, and secretory cells such as the
uterine UV1 cells; UNC-31::GFP translational fusions localize to neuronal cell bodies, axonal
projections and to sites of synaptic contact, consistent with other dense-core vesicle proteins.
unc-37 encodes a transducin-like WD-repeat protein orthologous to Drosophila Groucho; unc-37
plays an essential role in embryonic and neuronal fate specification; unc-37 genetically interacts
with components of the transcriptional Mediator complex.
The unc-44 gene encodes an ankyrin-like protein required for proper sex myoblast and axonal
guidance during development.
unc-49 encodes multiple subunits of a heteromeric GABA receptor; unc-49 activity is required for
postsynaptic GABA responsiveness and thus for normal regulation of locomotion; UNC-49::GFP
reporter fusions for at least two isoforms are expressed in dorsal and ventral head and body wall
muscles, with isoform-specific expression also seen in the sphincter muscle; UNC-49::GFP
subcellular localization is most prominent at neuromuscular junctions; in Xenopus oocytes and
mammalian tissue culture cells, two UNC-49 subunits, UNC-49B and UNC-49C, are able to form a
functional heteromeric GABA receptor.
unc-54 encodes a muscle myosin class II heavy chain (MHC B); UNC-54 is the major myosin heavy
chain expressed in C. elegans and is required for locomotion and egg-laying; in vivo and in vitro,
UNC-54 interacts with ITR-1, an IP3 receptor, and this interaction may provide a link between
calcium signaling and the muscle cytoskeleton; UNC-54 is a thick filament component that is
expressed in multiple muscle cell classes including body wall, intestinal, anal depressor, and
sphincter muscles as well as sex-specific muscles that develop postembryonically.
unc-58 encodes one of 44 C. elegans TWK (two-P domain K+) potassium channel subunits that
contain two pore-forming domains and four transmembrane domains; unc-58 was originally defined
by gain-of-function (gf) mutations that result in paralysis and a shortened (dumpy) body morphology
due to hypercontraction of body wall muscle; unc-58 gf mutations also result in constitutive egglaying; as loss of UNC-58 function via reversion or RNA-mediated interference (RNAi) results in
either no abnormalities or only a weakly uncoordinated phenotype, UNC-58 likely functions
redudantly with other TWK channels to regulate locomotion and egg-laying; UNC-58 is expressed
in motor neurons and interneurons.
unc-63
unc-63(x13)
ZZ13
unc-73
unc-73(ce362)
KG1278
unc-73(e936)
CB936
unc-73(ev802)
KG1397
unc-75
unc-75(e950)
CB950
vab-2
vab-2(ju1)
CZ4111
vhp-1
vhp-1(sa366)
JT366
Y23B4A.2(ok306
5) RB2263
Y23B4
A.2
Y58G8
A.1
Y59H11
AL.1
Y73F8
A.34
Y58G8A.1(ok177
0)
RB1502
Y59H11AL.1(ok1
598) RB1405
Y73F8A.34(ok16
44) RB1441
unc-63 encodes an alpha subunit of a levamisole-sensitive nicotinic acetylcholine receptor (LnAChR); UNC-63 is required for normal locomotion and regulation of egg-laying behavior, and
functions as a subunit of a ligand-gated ion channel that likely mediates fast actions of acetylcholine
at neuromuscular junctions and in the nervous system; when coexpressed with UNC-29 and LEV-1,
non-alpha L-nAChR subunits, the resulting multimer can form levamisole-gated channels; UNC-63
is expressed in body wall muscles, vulval muscles, and a large number of ventral cord neurons;
UNC-63 is a member of the UNC-38-like group of nAChR subunits.
unc-73 encodes a guanine nucleotide exchange factor (GNEF) similar to the Trio protein; UNC-73 is
required for vulval morphogenesis, for the migration of QL, QR, CAN, and hypodermal P cells, the
commissure outgrowth of D type motoneurons, and amphid axon outgrowth; UNC-73 has GNEF
activity for both CED-10 and MIG-2 in vitro; the requirement for UNC-73 in P cell migration can be
suppressed by transgenic overexpression of rho-1; UNC-73 activates several small GTPases: RHO-1
in P cell migration, and both CED-10 and MIG-2 in vulval morphogenesis, P cell migration, and
axon outgrowth.
unc-75 encodes an RNA-binding protein with two N-terminal RNA recognition motifs (RRMs), a
glutamine/asparagine-rich linker domain, and a third C-terminal RRM; UNC-75 is orthologous to
mammalian CELF/BrunoL proteins that control pre-mRNA splicing; unc-75 is expressed in all
neurons and in neurosecretory gland cells, and is required for normal modulation of GABA- and
acetylcholine-mediated neurotransmission; UNC-75 protein is found with other RRM proteins in
dynamic nuclear speckles, consistent with a role in alternative mRNA splicing; unc-75 mutations
can be rescued in vivo by a human unc-75 transgene, but not by exc-7 or W02D3.11, indicating that
UNC-75 acts on evolutionarily conserved but highly specific pre-mRNA substrates; both UNC-75
and EXC-7 are required in parallel for normal cholinergic neurotransmission.
The vab-2 gene encodes an ephrin molecule related to human ephrin B2 (OMIM:600527); VAB-2,
expressed primarily in neuronal cells, is a ligand for the VAB-1 ephrin receptor and plays a role in
embryonic cell movements, epidermal morphogenesis during later embryogenesis, and oocyte
maturation; VAB-2 synergizes with PTP-3, a LAR-like receptor tyrosine phosphatase, to regulate
morphogenesis.
vhp-1 encodes a MAP kinase phosphatase (MKP); VHP-1 activity is required for regulation of the
KGB-1/JNK-like MAPK-mediated stress response pathway.
Y23B4A.2 encodes a neuropeptide precursor that can produce a pyrokinin (PK)-like peptide and two
periviscerokinin (PVK)-like peptides; a synthetic peptide corresponding to the AFFYTPRI-NH2
sequence of Y23B4A.2 is able to bind and activate the G protein-coupled receptor encoded by
K10B4.4 when the latter is expressed in HEK293T cells; antibodies that recognize the protein
products of Y23B4A.2 stain two pairs of anterior neurons.
lgc-26 encodes a ligand-gated ion channel with similarity to the nicotinic acetylcholine receptors;
lgc-26 activity is required for endocytosis by coelomocytes; an LGC-26::GFP fusion protein is
expressed in coelomocytes and localizes to the cytoplasm.
Y59H11AL.1 gene
Temporarily Assigned Gene name