BIOC3800 Sensory Transducers

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BIOC3800Sensory Transducers

• Dr. J.A. Illingworth

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Course information

• There is a website to accompany this part of the
  course, http//www.bmb.leeds.ac.uk/illingworth/BIO
  C3800/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.

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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  several years out of date.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

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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."
• 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.

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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

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Common features (continued)

• In contrast to the previous slide, those sensors
  that monitor the bodys 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

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Sensory adaptation
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Compare and contrast

• High performance external sensors
• Vision
• Hearing and balance
• Smell
• Mechanosensors (some of these are slow, but
  muscle spindles and pressure transducers may
  provide rapid and precise responses to external
  events.)

• Slower, less adaptive internal mechanisms
• Taste (plus a family of related sensors lower in
  the GI tract that rarely reach consciousness)
• Monitoring systems for oxygen, carbon dioxide,
  glucose, small molecules, temperature, osmolarity
  and fluid flow have limited range and respond
  more slowly to stimulation.

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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.

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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

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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.

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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.

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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.

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Bacterial chemotaxis (3)
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Bacterial chemotaxis (4)
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Bacterial chemotaxis (5)

• Histidineaspartate-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 ?-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

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Bacterial chemotaxis (6)

• Some histidine - aspartate phosphorelay systems

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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 (CheYP) binds the switch
  protein FliM on the flagellar motor, causing
  temporary reversal in the direction of motor
  rotation.

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Bacterial chemotaxis (8)

• The phosphatase CheZ dephosphorylates CheYP and
  allows rapid signal termination.
• PBP periplasmic ligand binding protein

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Bacterial chemotaxis (9)

• Increased attractant inhibits autophosphorylation
  of CheA, which reduces CheYP 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.

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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.