BIOC3800 Exam 2008 John Illingworth’s Marking Scheme
Discuss the biological importance of sensory adaptation and outline
the adaptation mechanisms in a variety of biological transducers.
Adaptation is required for three main reasons: (1) biological transducers must operate over a
wide dynamic range, (2) changes in the input signal have greater biological significance than
a constant level, (3) selective filtering may be used to reject irrelevant noise while responding
to small but important signals. Animals are often interested in the first derivative of the input
signal with respect to time or space, rather than its absolute level. They may calculate higher
derivatives from the input – for example animals that navigate using smell need the second
derivative to analyse scent plumes effectively.
In addition to the low-level transducer adaptation systems described here, there are normally
downstream adaptation mechanisms within the central nervous system. Sensory transducers
normally have multiple adaptation systems which operate in parallel. I would not expect
students to describe all of these, but I hoped for a representative selection.
Bacteria: Methyl accepting chemotaxis proteins are plugged through the inner membrane. In
E. coli, there are periplasmic receptor proteins for attractants and repellents and a constitutive
MCP methylation system which reduces the sensitivity for attractants. MCP methylation level
tracks the attractant concentrations after a brief delay. This generates a first derivative output
and a wide dynamic range. Falling attractant concentrations cause MCPs to autophosphorylate
CheA, which in turn phosphorylates CheY and CheB. CheY switches flagellar drive motors to
clockwise mode (favouring tumbling) meanwhile CheB strips methyl groups from the MCPs,
increasing their sensitivity to attractant ligands.
Taste: GPCR receptors linked through phospholipase C β2 which hydrolyses phosphatidyl
inositol to yield IP3 and diacylglycerol. The IP3 releases internal Ca++ stores which open
TRPM5 channels, depolarising the cells and stimulating neurotransmitter and neuropeptide
release. Taste adapts to ongoing stimulation, but the mechanism is presently unknown.
Smell: GPCR receptors linked through adenyl cyclase open plasmalemma Ca++ channels.
Raised Ca++ opens chloride efflux channels and depolarises the plasmalemma. Adaptation
includes Ca++ / CAM inhibiting adenyl cyclase and Ca++ channels, GRK phosphorylating
olfactory receptor proteins, followed by -arrestin2 binding and receptor internalisation to
storage vesicles via clathrin-mediated endocytosis.
Vision: All species use retinal isomerisation as the initial detector, and receptor bleaching
provides a basic adaptation mechanism which reduces the number of receptor molecules at
high light intensities. Transduction and adaptation mechanisms differ between mammals
(where the sensors are hugely modified primary cilia) and insects (where the sensors are
modified microvilli). Mammalian rods and cones are depolarised in the dark and secrete the
inhibitory neurotransmitter glutamate, whereas insect receptors are polarised in the dark and
only secrete in response to light.
In mammals, in the dark, there is a high concentration of cGMP in the rod outer segments.
cGMP keeps a ligand-gated TRP channel open in the plasmalemma, leading to rapid entry of
sodium ions which partially depolarises the cell [-30mV]. Rhodopsin is a 7-transmembrane
helix integral membrane protein plugged through the disc membranes. The chromophore is
buried deep in the lipid bilayer. Key interactions take place on the cytosolic side of the disc
membrane.
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Photoexcited rhodopsin binds to a G-protein transducin. This is repeated several hundred
times, hugely amplifying the original signal. GTP for GDP exchange activates transducin. Tα
subunits dissociate from the G-protein and activate a cGMP phosphodiesterase on the disc
membrane. The phosphodiesterase provides a second stage of signal amplification.
The concentration of cGMP falls, closing the sodium channels. cGMP binding is a highly
cooperative process, Hill coefficient = 3. The rod outer membrane hyperpolarises [-70mV],
and the internal calcium concentration falls. The synaptic body stops secreting glutamate,
thereby activating bipolar cells within the retina. The fall in calcium concentration stimulates
guanyl cyclase, restoring the cGMP concentration as part of the adaptation process.
Tα subunits bound to phosphodiesterase hydrolyse GTP and terminate their own activity.
Rhodopsin kinase phosphorylates photoactivated rhodopsin on the cytosolic surface of the
discs. Arrestin binds to phosphorylated rhodopsin and blocks further transducin binding.
Recoverin binds calcium and blocks rhodopsin phosphorylation in the dark.
feature
mammals
drosophila
photoreceptor
rod & cones (modified cilia)
rhabdomeres (microvilli)
dark condition
depolarised, secreting glutamate
polarised, not secreting
initial effect of
light
meta-rhodopsin II activates
transducin (a G protein)
meta-rhodopsin II activates G
protein
first termination
opsin and trans retinal dissociate
no retinal dissociation
retinal recycling
slow, involves pigment cells
fast, red light reforms cis-rhodopsin
G protein
releases free Gαt subunits
releases free Gαq subunits
target enzyme
cGMP phosphodiesterase
phospholipase C β4
response
termination
RGS-9 + PDE-γ regulate GTPase
activity
RGS(?) + PLC regulate GTPase
activity
second
messenger
cGMP falls on illumination
diacylglycerol (?) rises on
illumination
plasmalemma
cGMP-gated Na+ / Ca++ TRP
channels close
DAG-gated (?) TRP channels open
effect of light
PRC hyperpolarises, stops secreting PRC depolarises, starts secreting
light adaptation 1
Ca++ falls; guanyl cyclase activity
rises
Ca++ rises; initial +ve feedback
within microvillus
light adaptation 2 rhodopsin kinase inactivates opsin
rhodopsin kinase inactivates opsin
light adaptation 3 arrestin closes down rhodopsin
arrestin closes down rhodopsin
light adaptation 4
translocate arestin, transducin and
recoverin between compartments
translocate proteins between
compartments
light adaptation 5
switch from low resolution rods to
less sensitive more detailed cones
all rhabdomeres have similar
sensitivities – no colour vision
Ca++-dependent movement of
pigment granules
light adaptation 6 close pupil
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The vertebrate visual system is primarily looking for spots and edges, and ignores large areas
of constant light intensity. Images that are artificially fixed on the retina gradually fade away.
Hearing: the basic transduction mechanism with a separate endolymph compartment and
mechanically gated ion channels is common to insects and vertebrates. Most vertebrates can
perform audio spectrum analysis in the cochlea, but only mammals and crocodilians have a
frequency-selective amplification system.
The mammalian cochlea has a single row of inner hair cells and three rows of outer hair cells.
The detector ends are bathed in endolymph and there is an endocochlear potential. Both
groups of cells have stereocilia bundles (microvilli) with mechanically gated ion channels
which are opened by protein tip links as the stereocilia sway in response to sound vibrations.
The inner cells are sensory, but the outer cells are motile and provide frequency selective
amplification. They use the high-speed motor protein prestin to track individual sound
vibrations and overcome the damping in the basilar membrane. Multiple adaptation
mechanisms include (1) fast adaptation [~1msec] probably a direct effect of Ca++ entry on
myosin conformation, (2) slow adaptation [~20msec] actomyosin-based motor adjusts tip link
tension, (3) the amplification by the outer hair cells can be selectively adjusted by the brain,
(4) small muscles in the middle ear can be relaxed to protect the sensitive cochlea from
mechanical damage by loud noises.
Touch: multiple mechanoreceptor genes (usually TRP proteins) with poorly characterised
adaptation mechanisms. We did not spend much time on this.
Temperature: No transducer adaptation mechanism that I am aware of, but there are multiple
TRP receptor proteins with a variety of trigger points and steep temperature response curves
which cover the entire physiological range.
John Illingworth
June 2008
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