BIOC3800 Exam 2006 John Illingworth’s Marking Scheme
Discuss the roles of motor proteins in sensory transduction and
adaptation.
It is not possible to describe the adaptation mechanisms without referring 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.
The lecture “handout” was a website, with an electronic reading list and clickable 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:
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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
The diverse roles of motor proteins were repeatedly stressed during the lectures, not only in
relation to transduction and adaptation, but also in the correct assembly of the transduction
systems. Students were told to prepare for a very general examination question where they
would be able to select their own examples. I would only expect them to recall a small part of
the following material.
Bacterial chemotaxis: 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 (methylesterase), CheR, CheW,
CheY, CheZ, reversing the rotary flagellar motor, tumbling and free swimming.
Baker MD, Wolanin PM, Stock JB. (2006) Signal transduction in bacterial chemotaxis.
BioEssays 28(1), 9-22.
Wadhams GH and Armitage JP (2004) Making sense of it all: bacterial chemotaxis. Nat
Rev Mol Cell Biol 5, 1024-1037.
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.
Although in one sense the motor response is the ultimate output from the transduction system,
it is also an integral part of the transduction mechanism, moving the bacterium to a new
location from where it can sense its environment. In the absence of motion, the MCP system
would generate a constant signal, MCP methylation would accurately track the attractant
concentration, there would be no first derivative output and the transducer sensitivity would
be zero.
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Taste and smell: I am not aware of any established role for motor proteins in taste or smell
transduction and adaptation.
Hearing: The mammalian cochlea contains both inner and outer hair cells. The inner row
have limited motility but are the most sensitive transducers. The outer cells are highly motile
and respond to nervous stimulation. They are probably involved in selective amplification or
attenuation of sounds. Both sets of hair cells are bathed in endolymph and are subject to an
endocochlear potential.
Fettiplace R and Hackney CM (2006) The sensory and motor roles of auditory hair cells.
Nature Reviews in Neuroscience 7(1), 19-29.
Chan DK and Hudspeth AJ (2005) Ca2+ current-driven nonlinear amplification by the
mammalian cochlea in vitro Nat Neurosci 8, 149-155.
Gillespie PG and Cyr JL (2004) Myosin-1c, the hair cell’s adaptation motor. Annu Rev
Physiol 66, 521-545.
Motor proteins are required for the correct assembly and ongoing maintenance of the auditory
transduction system: myosin III, myosin VI, myosin VIIA and myosin XVa
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. Outer 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.
Vision: Motor proteins are required for the correct assembly, maintenance and adaptation of
the visual transduction system. Kinesins are required for the construction of cilia, including
photoreceptors. Myosin III is present in mammalian retina and in Drosophila the related
NINAC functions in photoadaptation. Myosin VIIa is required for recycling of photoreceptor
disks and its absence in Usher syndrome leads to retinitis pigmentosa.
Burns ME and Arshavsky VY (2005) Beyond counting photons: trials and trends in
vertebrate visual transduction. Neuron 48(3), 387-401.
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.
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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.
Summary table of visual detection and adaptation mechanisms from the module website.
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
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