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SUMMARY: &quot\;Unifying disease mechanisms in hereditary spastic parapleg
 ia&quot\; - Dr Evan Reid\, Cambridge Institute for Medical Research and De
 partment of Medical Genetics\, Addenbrooke's Hospital\, UK
DTSTART:20151216T120000Z
DTEND:20151216T130000Z
UID:TALK62831@talks.cam.ac.uk
CONTACT:Shannon Tinley-Browne
DESCRIPTION:Hereditary spastic paraplegias (HSPs) are genetic conditions c
 haracterised by distal axonal degenerations.  Many of the genes mutated in
  HSP encode proteins involved in membrane traffic processes\, with subsets
  involved in ER shaping\, endosomal tubule fission and lysosomal function.
  No pathway unifying these seemingly distinct pathological subgroups has b
 een identified. This talk focuses on the most commonly mutated HSP protein
 \, spastin and its interactor IST1.  I will present our work showing that 
 endosomal IST1 and an ER-localised isoform of spastin (M1-spastin) interac
 t to define ER-endosome contacts that control endosomal tubule fission. Co
 nsequent defects in receptor sorting cause abnormal lysosomal enzyme traff
 ic\, resulting in abnormal lysosomal morphology\, including in patient fib
 roblasts and neuronal cell models.  Furthermore\, we observed a similar ly
 sosomal abnormality in cellular models of other HSPs associated with abnor
 mal ER-shaping. As well as identifying a new role for ER-mediated endosoma
 l tubule fission in controlling lysosomal function\, by linking these proc
 esses we have identified a pathway that incorporates all classes of HSP pr
 oteins involved in membrane traffic. We propose this is the central pathwa
 y of HSP pathogenesis. 
LOCATION:Brain Repair Centre\, Forvie Site\, Robinson Way
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