BIOC3800 Exam 2007 John Illingworth’s Marking Scheme

Discuss the roles of primary cilia in sensory transduction.

The lecture course covered cilia in general: centrosomes and basal bodies, 9+2 microtubules in motile cilia and 9+0 microtubules in non-motile primary cilia, roles of kynesin and dynein in cilia assembly, bending and recycling. Many eukaryotic cells have a primary cilium. These were once considered to be vestigial, but are now recognised as important structures. We distinguished between eukaryotic cilia and bacterial flagellae,noted that mutations in cilia proteins may produce pleiotropic changes across several sensory modalities (e.g. Bardet-Biedl syndrome, Usher syndrome) and eventually discussed four sense organs in greater detail:

  • Flow sensors in kidneys, various exocrine glands, bones and teeth
  • Assembly of stereocilia bundles in auditory hair cells.
  • Vertebrate photoreceptors
  • Vertebrate smell

Students were expected to read the relevant literature. The course website has extensive links to recent reviews and original papers. During lectures we used normally used diagrams from recent papers, accessed on line, rather than preparing new figures for this particular course. Students were advised to spend 3 hours private study per lecture reading references, but it seems from their answers that very few of them actually followed this advice.

Flow sensors: (kidney tubules, bile ducts, pancreatic ducts, internal canals in bones and teeth) Bending of primary cilia is used to monitor fluid flows via changes in the intracellular calcium concentration. This is used to correctly align subsequent cell divisions in relation to the tubular lumen, and also allows hard tissues to grow correctly in response to mechanical stress. Over or under expression of the relevant genes leads to polycystic kidney disease.Related defects are sometimes seen in other tissues.

Hearing:The primary cilium (kinocilium) isneeded for the correct orientation and assembly of the hair cell bundles – there is no direct role for cilia in hearing transduction, which is performed bystereocilia (microvilli).Give credit for a reasonable description of the cochlear amplifier and hearing transduction mechanisms, especially if the student makes it clear that the cilium is required for assembly rather than transduction.

Vision:The photoreceptor compartments of vertebrate rod and cone cellsare hugely modified primary cilia.[Insects use a different visual transduction system based on microvilli.]Defects in vertebrate ciliary proteins (e.g. kinesin-2, usherin) lead to defective phototransducer assembly and maintenance.Material is continuously lost from the distal ends of rod cells and phagocytosed by cells in the retinal pigment layer. Give credit for a reasonable description of the visual transduction and adaptation mechanisms, especially where these are linked to ciliary functions.

Smell:Specific chemoreceptors located on the sensory cilia of olfactory receptor neurons are linked through G-proteins to adenyl cyclase. Receptor activation raises cAMP which activates cyclic nucleotide-gated calcium channels, increasing the calcium concentration within the cilia. This in turn opens calcium-gated chloride channels, leading to chloride efflux and depolarisation. The distal ends of olfactory cilia lack the two central microtubules and are non-motile. These are not true primary cilia, but they are closely related to them.

It was not necessary to write about all four systems to achieve a good mark. Students were expected to know what primary cilia are, and their relationship with centrosomes and basal bodies, and how they differ from normal, motile cilia. The ciliary assembly and maintenance systems are used both for cilia and for the sensors derived from them, so mutations affecting cilia genes also have widespread effects on sensory transduction.

A discussion of polycystic kidney disease or Usher Syndrome or any of the numerous other ciliary diseases would have been relevant to this answer.

This question provided an opportunity to write about the transduction process itself in one or more of these sense organs, describing how the transducers sense, how they are maintained and how they adapt to changing inputs. There are similarities between the transduction systems in different sense organs, reflecting their common evolutionary origin, and this would also have been considered relevant.

The topic was clearly flagged up in the lectures, and students who had read the some of the recommended papers, as well as the course website, should have found this an easy question to answer.

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