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Roles of spastic paraplegia proteins in formation of axonal ER in Drosophila

Dates:11 November 2014
Times:15:30 - 17:00
What is it:Seminar
Organiser:Faculty of Life Sciences
Who is it for:University staff, Current University students
Speaker:Dr Cahir O'Kane
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  • In category "Seminar"
  • In group "(BMH) Fly Club Seminar Series"
  • By Faculty of Life Sciences

The sheer length of motor axons requires significant engineering for the formation and maintenance of axonal structures. Failures of this maintenance are seen in the Hereditary Spastic Paraplegias (HSPs), which are characterised by spasticity and weakness of the lower limbs, and degeneration of longer upper motor axons. To date over 40 causative Spastic Paraplegia Genes (SPGs) have been identified. Several encode endoplasmic reticulum membrane proteins, some of which contain intramembrane hairpin structures that curve and help to model ER membrane. Two of these protein families, reticulons and REEPs, are together required for formation of most tubular ER in yeast. To test the model that these protein families are required for formation or maintenance of tubular axonal ER, we have developed markers for axonal ER in Drosophila, and generated and analyzed mutant genotypes that lack one or more members of these protein families.

In contrast to most rough ER markers, some of the intramembrane hairpin-containing proteins we have tested localise very strongly to axons, as do other smooth ER markers that we have tested, implying wide occurrence of ER in axons. Drosophila that lack single or multiple intramembrane hairpin proteins show a range of axonal ER phenotypes, thus supporting roles for these proteins in formation of axonal ER, and suggesting that changes in axonal physiology that result from ER disruption may underlie HSP disease mechanisms.

We have therefore established Drosophila motor axons as a system for assaying the organisation of axonal ER, and the roles of spastic paraplegia genes in this process. This should allow additional and newly identified HSP genes to be tested for such roles, either singly or in combination with others. The recovery of phenotypes with major disruption of axonal ER should also allow the physiological roles of this compartment to be tested.

O'Sullivan, NC, Jahn, TR, Reid, E, O'Kane, CJ, (2012) Reticulon-like-1, the Drosophila orthologue of the hereditary spastic paraplegia gene reticulon 2, is required for organization of endoplasmic reticulum and of distal motor axons. Hum Mol Genet. 21: 3356-65.

Yalçin, B., O’Kane, C.J. (2013). Maintaining Long Supply Lines: Axon Degeneration and the Function of Hereditary Spastic Paraplegia Genes in Drosophila. In: Drosophila melanogaster models of motor neuron disease (ed R Cauchi), Nova Science Publishers.

Speaker

Dr Cahir O'Kane

Organisation: University of Cambridge

  • http://www.gen.cam.ac.uk/research-groups/okane

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Sanjai Patel

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sanjai.patel@manchester.ac.uk

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