BIOC3800 Exam 2005 John Illingworth’s Marking Scheme
Discuss with examples the biochemical mechanisms responsible for
sensory adaptation.
The lecture “handout” was an electronic reading list, with links to key papers. Students were
expected to read a reasonable proportion, and advised to concentrate on the biochemical
mechanisms responsible for the following features of biological transducers:







very sensitive
huge dynamic range
negative feedback systems
adaptation to ongoing stimuli
report changes rather than the steady state
selection and filtering of information from the beginning
conversion from analog to digital encoding at an early stage of the transduction pathway
It is not possible to describe the adaptation mechanisms without refering to the underlying
transduction processes, so 50% of the marks are for adaptation and 50% for transduction. The
students had a lot of work to do, and a lot of information to remember, so I was relaxed about
minor errors and omissions. The question did not specify how many examples they should
give, and with more examples I would expect less detail about each one.
Bacterial chemotaxis:
Wadhams GH and Armitage JP (2004) Making sense of it all: bacterial chemotaxis. Nat
Rev Mol Cell Biol 5, 1024-1037.
A good answer would include the basic transduction pathway in E. coli or B. subtilis (which
are partly the opposite way round) including periplasmic binding proteins, methyl accepting
chemotaxis proteins, CheA, CheB, CheR, CheW, CheY, CheZ, reversing the rotary flagellar
motor, tumbling and free swimming.
Students should realise that MCPs may combine several contradictory input signals, and that
the degree of methylation is the adaptation mechanism, that tracks and compensates for the
net attractant signal. The delays inherent in the feedback system through CheB allow CheY to
transduce the first derivative of the attractant signal, and this is used to control the motor.
Taste:
Zhang Y et al (2003) Coding of sweet, bitter, and umami tastes: different receptor cells
sharing similar signaling pathways. Cell 112, 293-301.
Prawitt D et al (2003) TRPM5 is a transient Ca2+-activated cation channel responding to
rapid changes in [Ca2+]i Proc Natl Acad Sci U S A 100, 15166-15171.
Sweet, bitter, and umami taste receptors are distinct GPCRs signaling through PLC2 which
increases intracellular [Ca++] and activates TRPM5, which is a monovalent cation channel.
Excess Ca++ is inhibitory, and this contributes to adaptation, which is not well understood.
TRPM5 inherently responds to rapid changes in [Ca++] rather than the steady state.
page 1
Olfaction:
Matthews HR and Reisert J (2003) Calcium, the two-faced messenger of olfactory
transduction and adaptation. Curr Opin Neurobiol 13, 469-475.
Olfactory transduction takes place in the cilia of the olfactory receptor cells, each of which
expresses only one from a large family of odourant receptors. Odourant binding activates
adenyl cyclase through a G protein system. The rise in cAMP concentration opens cyclic
nucleotide-gated channels, and an influx of Na+ and Ca++ initiates the electrical response to
odour stimulation.
Increased ciliary [Ca++] has two opposing effects: activation of an excitatory Cl− channel, and
negative feedback on two stages of the odour transduction mechanism. Ca++ calmodulin
rapidly inhibits the calcium entry channel, and CaM kinase slowly reduces the activity of
adenyl cyclase. These two processes are thought to explain fast and slow components of the
olfactory adaptation mechanism
Hearing:
Fettiplace R and Ricci AJ (2003) Adaptation in auditory hair cells. Curr Opin Neurobiol
13, 446-451.
Gillespie PG and Cyr JL (2004) Myosin-1c, the hair cell’s adaptation motor. Annu Rev
Physiol 66, 521-545.
Chan DK and Hudspeth AJ (2005) Ca2+ current-driven nonlinear amplification by the
mammalian cochlea in vitro Nat Neurosci 8, 149-155.
The mammalian cochlea contains both inner and outer hair cells. The inner row are the most
sensitive transducers, but the outer rows are more motile. The outer cells respond to nervous
stimulation and may be involved in selective amplification or attenuation of sounds. Both sets
of cells are bathed in endolymph and subject to an endocochlear potential.
Mechanical bending of hair bundles towards their tallest edge opens mechanically gated ion
channels near the tips of the component stereocilia. This allows an influx of K+ and Ca++ ions
that depolarize the hair cell. Deflection of the stereocilia exerts tension on the tip links that
transmit force to the mechanoelectrical transducer TRPA1 channel. To keep the system within
a narrow operating range these channels are subject to multiple Ca++-controlled mechanisms
of adaptation.
Fast adaptation requires direct interaction of Ca++ with TRPA1 channels to modulate their
open probability. The diffusion distance is only 15–35 nm so this process completes in 1
msec. This fast Ca++-dependent channel reclosure may be involved in amplification, which
requires cycle-by-cycle force generation. Hair cell bodies are also motile and contain prestin,
whose shape responds to membrane potential in about 10 msec. Slow adaptation takes 20
msec and requires a Ca++–dependent motor, myosin-1c, to tension the elastic elements in
series with the TRPA1 channel. cAMP shifts the “channel open” probability along the
displacement axis, with no effect on fast adaptation, perhaps through phosphorylation of the
TRPA1 channel or the myosin motor by protein kinase A.
In addition, reflex relaxation of the muscle that tensions the maleus, incus and stapes protects
the delicate hearing mechanism in very noisy environments.
page 2
Vision:
Fain GL et al (2001) Adaptation in vertebrate photoreceptors. Physiol Rev 81, 117-151.
Hardie RC & Raghu P (2001) Visual transduction in Drosophila. Nature 413, 186-193.
Cronin MA et al (2004) Light-dependent subcellular translocation of Gqa in Drosophila
photoreceptors is facilitated by the photoreceptor-specific myosin III NINAC. J Cell Sci
117, 4797-4806.
mammals
drosophila
photoreceptor
rod & cones (modified cilia)
rhabdomeres (microvilli)
dark condition
depolarised, secreting glutamate
polarised, not secreting
initial light effect
meta-rhodopsin II activates
transducin
meta-rhodopsin II activates G
protein
first termination
opsin and trans retinal dissociate
no dissociation
retinal recycling
slow, involves pigment cells
fast, involves red light
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
2nd messenger
cGMP falls on illumination
DAG (?) rises on illumination
plasmalemma
cGMP-gated TRP channels close
DAG-gated (?) TRP channels open
final light effect
PRC hyperpolarises, stops secreting PRC depolarises, starts secreting
light adaptation 1
Ca++ falls; guanyl cyclase activity
rises
Ca++ rises; +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 proteins between
compartments
translocate proteins between
compartments
light adaptation 5
switch from rods to less sensitive
cones
all rhabdomeres have similar
sensitivities
Ca++-dependent movement of
pigment granules
light adaptation 6 close pupil
page 3