BIOC3800
Sensory Transducers
Dr. J.A. Illingworth
Course information
• There is a website to accompany this part of the course,
http://www.bmb.leeds.ac.uk/illingworth/BIOC3800/index.htm
with model answers, self-assessment tests and clickable
links to recent papers and other sources of information.
• Examination questions on sensory transduction will allow
you to select your own illustrations and examples, but we
expect you to supply details about examples you select.
• Aim to spend about 3 hours private study on each lecture,
reading papers and preparing summary diagrams that could
be produced in the written examinations.
• Try to see the big picture without becoming bogged down in
a mass of very minor details.
Some textbooks
• Many general physiology texts include an account of the special
senses, but unavoidable production delays mean that even the
latest textbooks are several years out of date. We suggest:
• Principles of Anatomy and Physiology. Tortora GJ & Derrickson BH
(Wiley, 2008.) ISBN 9780470233474 there is a simple account in
chap. 17, older editions are also useful
• Medical Physiology. Boron WF and Boulpaep EL (eds) (W.B.
Saunders, 2005.) ISBN 1416023283 more detail in chap. 13
• Human Physiology. Sherwood L (Brooks/Cole, 2010) ISBN
9780495826293 see chapter 6 on special senses
• Principles of Neural Science. Kandel ER et al (McGraw-Hill, 2000.)
ISBN 0838577016 see part V - an excellent book, but getting dated
• Fundamental Neuroscience. Squire LR et al (Academic Press,
2008.) ISBN 9780123740199 detailed account in chapters 24 – 27
Previous examination questions
•
This is a large and rapidly changing field, so we set wide-ranging examination
questions that allow you considerable choice. We expect you to illustrate your
answers with details of the specific examples that you select.
•
2005: "Discuss with examples the biochemical mechanisms responsible for
sensory adaptation."
2006: "Discuss the roles of motor proteins in sensory transduction and
adaptation."
2007: "Discuss the roles of primary cilia in sensory transduction."
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•
•
•
•
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2008: "Discuss the biological importance of sensory adaptation and outline the
adaptation mechanisms in a variety of biological transducers."
2009: "Describe with examples how the basic molecular architecture of primary
cilia and microvilli has been adapted to create a wide range of sensory
transducers."
2010: "Compare and contrast the signal transduction mechanisms in sense
organs that monitor the external world with those that monitor the internal
condition of the body. Please illustrate your answer with some specific
examples."
The question in 2011 will follow a similar pattern to previous years.
Common features of sensory transducers
Sensory transducers report biologically relevant information
to their owners. External sensors often:
• are very fast
• are very sensitive
• adapt to ongoing stimuli
• have a huge dynamic range
• incorporate local feedback loops
• report changes rather than the steady state
• select and filter information from the start of the path
• convert from analog signals to faster, low-noise digital
encoding at an early stage of the transduction pathway
Common features (continued)
In contrast to the previous slide, those sensors that
monitor the body’s internal environment often
•
•
•
•
•
•
have more time
require less sensitivity
respond in a narrow physiological range
show less adaptation towards ongoing situations
form part of "whole body" negative feedback systems
have less need to filter the raw information to remove
unwanted noise
• are more likely to include slower analog systems rather
than faster digital signaling components
Sensory adaptation
100
90
80
70
response
60
50
< ten-fold change in sensitivity >
40
30
20
10
0
0
0.5
1
1.5
log (stimulus)
2
2.5
3
Compare and contrast…
High performance
‘external’ sensors
• Vision
Slower, less adaptive
‘internal’ mechanisms
• Smell
• Taste (plus a family of
related sensors lower in
the GI tract that rarely
reach consciousness)
• Mechanosensors (some
of these are slow, but
muscle spindles and
pressure transducers
may provide rapid and
precise responses to
external events.)
• Monitoring systems for
oxygen, carbon dioxide,
glucose, small molecules,
temperature, osmolarity
and fluid flow have limited
range and respond more
slowly to stimulation.
• Hearing and balance
Closed loop control systems
Every closed loop system keeps a controlled variable C as close as possible
to some reference value R despite interference by an external load L which
disturbs the result. In order to achieve its objective the system subtracts C
from R so as to generate an error signal, E. This error signal regulates the
flow of material or energy M into the controlled system so as to minimise E
and compensate for the effects of the external load.
Control systems (2)
Every closed loop system needs a reference value which
provides a target to aim for. This is always true, even for
complex biological control systems, although sometimes
the targets are obscure. There is no requirement for the
target to stay constant, although they often do.
• constant reference value but varying load: thermostat
• varying reference but constant load: audio amplifier
• varying reference and varying load: brain & muscles
Control systems (3)
• Biological reference values may be genetically
determined, for example through the amino acid
sequences of regulatory proteins, which define their
binding constants for allosteric effectors. Behavioural
targets for an organism might also reflect the genetically
programmed "wiring diagram" for the central nervous
system.
• For “external” sensory transducers the reference value
is definitely NOT constant, because it is the input signal
from the outside world. These transducers commonly
track this varying input signal, and thereby generate first
derivative, logarithmic and filtered information more
appropriate to the needs of the organism.
Bacterial chemotaxis (1)
• Bacteria are too small to sense chemical gradients directly.
• They discover the best direction by making small random
movements in arbitrary directions, and keep going for longer
if things improve.
• E. coli cells have typically half a dozen flagellae, which are
attached to the cell by extremely flexible universal joints,
and independently rotated by motors in the cell wall.
• The flagellae are "handed" like corkscrews. If they all rotate
anti-clockwise (viewed from the far end) they mesh together
and form an efficient propulsive unit
• If one or more flagellae adopt a clockwise rotation then the
flagellar bundle flies apart and the cell tumbles randomly in
the growth medium.
Bacterial chemotaxis (2)
• Wadhams & Armitage (2004) Making sense of it all:
Bacterial Chemotaxis. Nature Reviews in Molecular Cell
Biology 5, 1025 – 1037.
• Baker et al (2006) Signal transduction in bacterial
chemotaxis. BioEssays 28.1, 9 – 22.
• Thomas et al (2006) The Three-Dimensional Structure of
the Flagellar Rotor from a Clockwise-Locked Mutant of
Salmonella enterica Serovar Typhimurium. J. Bacteriology,
188(20), 7039-7048.
• Rao et al (2008) The three adaptation systems of Bacillus
subtilis chemotaxis.Trends in Microbiology 16, 480 – 487.
Bacterial chemotaxis (3)
Bacterial chemotaxis (4)
Bacterial chemotaxis (5)
• Histidine–aspartate-phosphorelay systems
• HAP systems have at least two components — a dimeric
histidine protein kinase (HPK) and a response regulator
(RR). The Arabidopsis thaliana genome has 16 genes for
HPK and 24 RR homologues.
• HAP systems rely on the trans-autophosphorylation of a His
residue that resides in one monomer of the HPK dimer by
the γ-phosphoryl group of an ATP molecule that is bound to
the kinase domain of the other monomer.
• This phosphoryl group is then transferred to an Asp residue
on a separate RR protein to alter its activity and generate a
response
Bacterial chemotaxis (6)
• Some histidine - aspartate phosphorelay systems
Bacterial chemotaxis (7)
• Chemotactic signals are detected by transmembrane
chemoreceptors — the methyl-accepting chemotaxis
proteins (MCPs).
• An adaptor protein, CheW, helps link the MCPs to the
cytoplasmic HPK, CheA, and two RRs compete for
binding to CheA.
• One RR is a single-domain, flagellar motor binding
protein, CheY, whereas the other, CheB, functions as a
methylesterase and controls the adaptation of the MCPs.
• Phosphorylated CheY (CheY–P) binds the switch protein
FliM on the flagellar motor, causing temporary reversal in
the direction of motor rotation.
Bacterial chemotaxis (8)
• The phosphatase CheZ dephosphorylates CheY–P and
allows rapid signal termination.
• PBP – periplasmic ligand binding protein
Bacterial chemotaxis (9)
• Increased attractant inhibits autophosphorylation of CheA,
which reduces CheY–P and hence the frequency of motor
switching. This causes the bacterium to swim in a positive
direction for longer.
• CheB phosphorylation and methylesterase activity is also
reduced, which allows the constitutive methyltransferase
CheR to methylate the MCPs.
• Highly methylated MCPs are better able to stimulate CheA
autophosphorylation, which returns to the pre-stimulus level.
• MCP methylation therefore tracks the attractant level after a
slight delay. This allows the system to calculate the vital first
derivative of the attractant concentration.
Bacterial chemotaxis (10)
• Regulation of chemotaxis in B. subtilis is more complex
than in E. Coli, and three overlapping control systems
are involved.
• CheY-P binding causes counter-clockwise rotation of the
motor in B. subtilis and clockwise rotation in E. coli
• Counter-clockwise rotation correlates with runs and
clockwise rotations with tumbles in both organisms
• In E. coli, binding of attractant to the receptors inhibits
CheA kinase activity, thereby reducing CheY-P
concentrations and increasing the likelihood of a run.
• In B. subtilis, attractant activates the CheA kinase,
thereby increasing CheY-P concentration and increasing
the likelihood of a run.