Using Drosophila spastic paraplegia genes to dissect formation of axonal endoplasmic reticulum

The length of motor axons requires significant engineering for their formation and maintenance. Failures of this maintenance are seen in the Hereditary Spastic Paraplegias (HSPs), characterised by lower limb weakness, and degeneration of longer upper motor axons. To date over 50 causative Spastic Paraplegia Genes (SPGs) have been identified. Several encode endoplasmic reticulum membrane proteins, with intramembrane hairpin structures that curve and model ER membrane. Two of these protein families, reticulons and REEPs, are together required for formation of most tubular ER in yeast. To test whether they are also required for formation or maintenance of axonal ER, we have developed suitable markers in Drosophila, and analyzed mutants that lack members of these protein families. We find differing effects of loss-of-function genotypes, ranging from no detectable effect, to more severe but partially penetrant effects in multiple mutants, showing some redundancy of function.
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 will allow additional and newly identified HSP genes to be tested for such roles, either singly or in combination with others.


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Dr Jemeen Sreedharan
The Brian Heap Seminar Room