Cell Communication
Lecture 14
Outline
▪ Review of Photosynthesis
– Finish up Cam plants
▪ Cell-Cell Communication
– Local vs Long distance
– Three Stages of Signaling
▪ Reception
▪ Transduction
▪ Response
Photosynthesis - Overview
▪ “Fixing” Carbon
▪ 6 CO2 + 12 H2O + Photons (light energy) C6H12O6 + 6 O2 + 6 H2O
▪ A redox reaction:
becomes reduced
Energy  6 CO2  6 H2O
C6 H12 O6  6 O2
becomes oxidized
Figure 10.UN01
CO2
H 2O
Light
NADP
ADP
+ Pi
Light
Reactions
Calvin
Cycle
ATP
NADPH
Figure 10.6-4
Chloroplast
O2
[CH2O]
(sugar)
Photosynthesis – Light Dependent Reaction –
Electron flow
Photosynthesis – C3 Reveiw
The C4 pathway
C4 leaf anatomy
Photosynthetic
cells of C4
plant leaf
Mesophyll
cell
PEP carboxylase
Mesophyll cell
Bundlesheath
cell
Oxaloacetate (4C)
Vein
(vascular tissue)
PEP (3C)
ADP
Malate (4C)
Stoma
Bundlesheath
cell
CO2
ATP
Pyruvate (3C)
CO2
Calvin
Cycle
Figure 10.20
Sugar
Vascular
tissue
Photosynthesis – Cam plants
▪ Evolved to conserve water
– Many succulents, cactus, pinapple
▪ Sub set of C4 photosynthetic plants
▪ Close their stomata during the day
▪ Open them at night
–
–
–
–
Lets in CO2
Fixes it in the same way that C4 plants do
However, malate gets stored in vacuoles
During the day it gets pumped back into the mesophyll cell and the
calvin cycle can proceed.
Sugarcane
Pineapple
C4
CAM
CO2
Mesophyll Organic acid
cell
CO2
1 CO2 incorporated
(carbon fixation) Organic acid
Night
Figure 10.21
CO2
CO2
Bundlesheath
cell
Calvin
Cycle
Sugar
(a) Spatial separation of steps
2 CO2 released
to the Calvin
cycle
Calvin
Cycle
Day
Sugar
(b) Temporal separation of steps
Cell Communication
▪ Essential for multicellular and
unicellular organisms
– There are universal mechanisms that
are conserved
– Communication is mostly through
chemical signals
▪ Fight or flight – release of
epinephrine
Cell-Cell Communication – Example –
Yeast
▪ Two mating types
– Type a and type a
▪ Different types locate each
other via secreted factors that
are specific to each type
Cell-Cell Com. – Signal Transduction Pathways
▪ A series of steps that
convert a signal on a cell’s
surface into a specific
cellular response
▪ Pathways are conserved
– Indicates that pathways
evolved in prokaryotes and
were later modified in
eukaryotes
Cell – Cell Com. – Local Signaling
▪ Cells in multicellular organisms communicate via chemical
messengers
▪ Animal and Plant cells have cell junctions
– Directly connect the cytoplasm of adjacent cells
▪ Local signaling
– Cells may communicate by direct contact or cell-cell recognition
– Local Regulator: messenger molecules that travel short distances
Plasma membranes
Gap junctions
between animal cells
(a) Cell junctions
Figure 11.4
(b) Cell-cell recognition
Plasmodesmata
between plant cells
Figure 11.5a
Local signaling
Electrical signal
along nerve cell
triggers release of
neurotransmitter.
Target cell
Secreting
cell
Local regulator
diffuses through
extracellular fluid.
(a) Paracrine signaling
Neurotransmitter
diffuses across
synapse.
Secretory
vesicle
Target cell
is stimulated.
(b) Synaptic signaling
Figure 11.5b
Cell-Cell Com. – Long-distance
signaling
Long-distance signaling
Endocrine cell
Blood
vessel
▪ Hormons are long distance messengers
– Cells that are supposed to respond to signals will
have specific receptors for that signal
Hormone travels
in bloodstream.
Target cell
specifically
binds
hormone.
(c) Endocrine (hormonal) signaling
Cell-Cell Com. – Three stages of cell signaling
▪ Reception
– Signal is received by specific cell surface molecules
▪ Transduction
– Signal is passed from molecule to molecule
▪ Response
– Targeted response to the signal is initiated
EXTRACELLULAR
FLUID
1 Reception
Receptor
Figure 11.6-1
Signaling
molecule
CYTOPLASM
Plasma membrane
EXTRACELLULAR
FLUID
1 Reception
CYTOPLASM
Plasma membrane
2 Transduction
Receptor
Relay molecules in a signal transduction
pathway
Figure 11.6-2
Signaling
molecule
EXTRACELLULAR
FLUID
1 Reception
CYTOPLASM
Plasma membrane
2 Transduction
3 Response
Receptor
Relay molecules in a signal transduction
pathway
Figure 11.6-3
Signaling
molecule
Activation
of cellular
response
Cell-Cell Com. – Three Stages - Reception
▪ A signaling molecule binds to a receptor protein
– Receptor is usually a membrane bound protein
– Causes a shape change
– Shape change is usually the first step in the transduction of the signal
▪ Receptor binds a LIGAND
– Binding is highly specific
Cell-Cell Com. – Three Stages – Reception –
Three types of Receptors
▪ G protein-coupled receptors
▪ Receptor tyrosine kinases
▪ Ion channel receptors
Cell-Cell Com. – Reception – G Protein Coupled
Receptors (GPCRs)
▪ The largest family of cell surface receptors
Signaling molecule binding site
▪ Works with the help of a G protein
– G protein acts like an on/off switch
▪ If GDP is bound to the G protein, it is inactive
Segment that
interacts with
G proteins
G protein-coupled receptor
Figure 11.7b
G protein-coupled
receptor
CYTOPLASM
1
Plasma
membrane
Activated
receptor
Enzyme
Inactive
enzyme
GTP
GDP
GDP
G protein
(inactive)
Signaling
molecule
2
GDP
GTP
Activated
enzyme
GTP
GDP
P
3
Cellular response
4
i
Cell-Cell Com. – Reception – G Protein Coupled
Receptors (GPCRs)
▪ Importance of G- Proteins
– ~800 different GPCRs
▪ Detect photons, hormones, growth factors, drugs, neurotransmitters…
– Implicated in many diseases
▪ Diabetes
▪ Blindness
▪ Allergies
▪ Depression
▪ Cardiovascular defects – Beta adrenergic receptors…
▪ Cancers
– 30% of Modern drugs target GPCRs
Cell-Cell Com. – Reception – Receptor Tyrosine
Kinases (RTKs)
▪ Receptors that attach phosphates to tyrosines
– Can trigger multiple pathways at once
– Often associated with cancers
Signaling
molecule (ligand)
Ligand-binding site
Signaling
molecule
a helix in the
membrane
Tyrosines
CYTOPLASM
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
(inactive monomers)
1
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Dimer
2
Activated relay
proteins
Figure 11.7c
3
Tyr
Tyr
P Tyr
Tyr P
Tyr
Tyr
P Tyr
Tyr P
Tyr
Tyr
P Tyr
Tyr P
6
Activated tyrosine
kinase regions
(unphosphorylated
dimer)
ATP 6 ADP
Fully activated
receptor tyrosine
kinase
(phosphorylated
dimer)
4
P Tyr
Tyr P
P Tyr
Tyr P
P Tyr
Tyr P
Inactive
relay proteins
Cellular
response 1
Cellular
response 2
Cell-Cell Com. – Reception – Receptor Tyrosine
Kinases (RTKs)
▪ Importance of RTKs
– 58 unique RTKs
– ~20 classes of RTKs
– Important for many growth factors
▪ Regulate growth and differentiation
– Cytokines (small signaling proteins that are important in immunity)
– Hormones
Cell-Cell Com. – Reception – Ligand-gated ion
channel
▪ Act as a gate, opening when the ligand binds
– When open, it allows specific ions to flow through a channel in the
receptor
– Na+ and Ca+ channels are examples
Figure 11.7d
1
Signaling
molecule
(ligand)
3
2
Gate
closed
Ligand-gated
ion channel receptor
Ions
Plasma
membrane
Gate closed
Gate
open
Cellular
response
Cell-Cell Com. – Reception – Ligand-gated ion
channel
▪ Importance of Ion gated channels
– Many neurotransmitters are Ligand-gated ion channels
– Many are the site at which anesthetic agents as well as ethanol act
– GABAA receptor
▪ Gamma-aminobutyric acid
▪ On of the chief neurotransmitters in the central nervous system
– GABA agonists – drugs that stimulate the GABA receptors, produce a sedative effect,
anti anxiety, muscle relaxants
▪ Ethanol, barbiturates (Luminal – antieplileptic, Phenobarbital- sedative),
benzodiazepins (Xanax, Ativan, Valium)
– GABA antagonists - stimulants
▪ Note: GABAB receptor is a GPCR
Cell-Cell Com. – Reception – Intracellular
Receptors
▪ Found in the cytosol or nucleus of target cells
– Usually activated by small or hydrophobic chemical messengers
▪ Steroids and thyroid hormones
– An activated hormone-receptor complex can directly turn on a gene
▪ A transcription factor – initiates and propagates gene transcription
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
DNA
Figure 11.9-1
NUCLEUS
CYTOPLASM
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
Figure 11.9-2
NUCLEUS
CYTOPLASM
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
Figure 11.9-3
NUCLEUS
CYTOPLASM
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
Figure 11.9-4
mRNA
NUCLEUS
CYTOPLASM
Hormone
(testosterone)
EXTRACELLULAR
FLUID
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
DNA
Figure 11.9-5
mRNA
NUCLEUS
CYTOPLASM
New protein
Cell-Cell Com. – Transduction
▪ Cascades of molecular interactions relay signals from
receptors to target molecules in the cell
– Usually involves multiple steps
– Can amplify a signal
▪ Just a few molecules can produce a large cellular response
– Multiple steps in the pathways provide opportunities for coordination and
regulation
▪ Can be controlled and various steps
Cell-Cell Com. – Transduction
▪ Cascades are usually made up of
proteins
– One protein activates another, which
activates another, which activates
another…
▪ Down the chain until the final protein that
produces the response is activated
– Each step the signal is transduced into a
different form
▪ Usually a shape change
Cell-Cell Com. – Transduction – Protein
Phosphorylation & Dephosphorylation
▪ Many pathways transmit the
signal via phosphorylation of
proteins in the chain
– Called Kinase Cascades
▪ Protein Kinase is an enzyme that
phosphorylates a protein
– Phosphate group comes from ATP
Signaling molecule
Receptor
Activated relay
molecule
Inactive
protein kinase
1
Active
protein
kinase
1
Inactive
protein kinase
2
ATP
P
Figure 11.10
ADP
P
Active
protein
kinase
2
PP
i
Inactive
protein kinase
3
ATP
P
ADP
Active
protein
kinase
3
PP
i
Inactive
protein
ATP
P
PP
i
ADP
P
P
Active
protein
Cellular
response
Cell-Cell Com. – Transduction – Second
Messengers
▪ First messenger is the ligand that binds to the receptor of a
specific pathway
▪ Second Messengers are small, nonprotein, water-soluble
molecules or ions that spread throughout a cell by diffusion
– They spread the message across the cell
▪ They are part of GPCR and RTK pathways
▪ Cyclic AMP and calcium ions are common second messengers
Cell-Cell Com. – Transduction – Second
Messengers – Cyclic AMP
• Cyclic AMP (cAMP) is one of the most widely used second
messengers
• Adenylyl cyclase, an enzyme in the plasma membrane,
converts ATP to cAMP in response to an extracellular signal
Figure 11.11
Adenylyl cyclase
Phosphodiesterase
Pyrophosphate
P
ATP
P
H2 O
i
cAMP
AMP
Cell-Cell Com. – Transduction – Second
Messengers – Cyclic AMP
▪ Many signal molecules trigger the formation of cAMP
▪ cAMP usually activates protein kinase A, which phosphorylates
various other proteins
▪ Further regulation of cell metabolism is provided by G-protein
systems that inhibit adenylyl cyclase
First messenger
(signaling molecule
such as epinephrine)
Adenylyl
cyclase
G protein
G protein-coupled
receptor
GTP
ATP
cAMP
Second
messenger
Figure 11.12
Protein
kinase A
Cellular responses
Cell-Cell Com. – Response
▪ Cell signaling leads to regulation of transcription or
cytoplasmic activities
– Sometimes referred to as output response
▪ Signal transduction leads to the regulation of one or more
cellular activities
▪ Response may occur in the cytoplasm or the nucleous
– Many signaling pathways regulate the synthesis of enzymes & proteins
by turning on or off genes
– Often, the final activated molecule in the pathway may functions as a
transcription factor
Growth factor
Reception
Receptor
Phosphorylation
cascade
Transduction
CYTOPLASM
Figure 11.15
Inactive
transcription
factor
Active
transcription
factor
P
Response
DNA
Gene
NUCLEUS
mRNA
Some pathways regulate the
activity of enzymes rather than
their synthesis
Reception
Binding of epinephrine to G protein-coupled receptor (1 molecule)
Transduction
Inactive G protein
Active G protein (102 molecules)
Inactive adenylyl cyclase
Active adenylyl cyclase (102)
ATP
Cyclic AMP (104)
Inactive protein kinase A
Active protein kinase A (104)
Inactive phosphorylase kinase
Active phosphorylase kinase (105)
Inactive glycogen phosphorylase
Active glycogen phosphorylase (106)
Response
Figure 11.16
Glycogen
Glucose 1-phosphate
(108 molecules)
RESULTS
Can result broad changes
like changes in cell shape
CONCLUSION
1 Mating
factor
activates
receptor.
Wild type (with shmoos)
formin
Fus3
Mating
factor G protein-coupled
receptor
Shmoo projection
forming
P
Fus3
GDP
Figure 11.17
GTP
2 G protein binds GTP
and becomes activated.
Fus3
Actin
subunit
P
Phosphorylation
cascade
Fus3
Formin
Formin
P
4 Fus3 phosphorylates
formin,
activating it.
P
3 Phosphorylation cascade
activates Fus3, which moves
to plasma membrane.
Formin
Microfilament
5 Formin initiates growth of
microfilaments that form
the shmoo projections.
Cell-Cell Com. – Response – Fine-tuning the
response
▪ There are four aspects of fine-tuning
–
–
–
–
Amplification of the signal (and thus the response)
Specificity of the response
Overall efficiency of response, enhanced by scaffolding proteins
Termination of the signal
Cell-Cell Com. – Response – Fine-tuning the
response - Amplification
▪ Enzyme cascades amplify the cell’s response
▪ At each step, the number of activated products is much
greater than in the preceding step
Cell-Cell Com. – Response – Fine-tuning the
response – Specificity and coordination
▪ Different kinds of cells have different collections of proteins
▪ These different proteins allow cells to detect and respond to
different signals
▪ Even the same signal can have different effects in cells with
different proteins and pathways
▪ Pathway branching and “cross-talk” further help the cell
coordinate incoming signals
Figure 11.18
Signaling
molecule
Receptor
Relay
molecules
Response 1
Cell A. Pathway leads
to a single response.
Activation
or inhibition
Response 2
Response 3
Cell B. Pathway branches,
leading to two responses.
Response 4
Cell C. Cross-talk occurs
between two pathways.
Response 5
Cell D. Different receptor
leads to a different
response.
Cell-Cell Com. – Response – Fine-tuning the
response – Scaffolding Proteins and Signaling
Complexes
▪ Large relay proteins to which other relay proteins are attached
– Can increase the signal transduction efficiency by grouping together
different proteins involved in the same pathway
– In some cases, may also help activate some of the relay proteins
Figure 11.19
Signaling
molecule
Plasma
membrane
Receptor
Scaffolding
protein
Three
different
protein
kinases
Cell-Cell Com. – Response – Fine-tuning the
response – Termination of the Signal
▪ If ligand concentration falls, fewer receptors will be bound
▪ Unbound receptors revert to an inactive state