INVESTIGADORES
FERNANDEZ Claudio Oscar
artículos
Título:
Synuclein interacts with the switch region of Rab8a in a Ser129 phosphorylation-dependent manner
Autor/es:
CLAUDIO O. FERNANDEZ
Revista:
NEUROBIOLOGY OF DISEASE
Editorial:
ACADEMIC PRESS INC ELSEVIER SCIENCE
Referencias:
Año: 2014 vol. 70 p. 149 - 161
ISSN:
0969-9961
Resumen:
Alpha-synuclein(αS)misfoldingisassociatedwithParkinson´sdisease(PD)butlittleisknownaboutthemechanismsunderlyingαStoxicity.Increasingevidencesuggeststhatdefectsinmembranetransportplayanimportantroleinneuronaldysfunction.HerewedemonstratethattheGTPaseRab8ainteractswithαSinrodentbrain.NMRspectroscopyrevealsthattheC-terminusofαSbindstothefunctionallyimportantswitchregionaswellastheC-terminaltailofRab8a.InlinewithadirectRab8a/αSinteraction,Rab8aenhancedαSaggregation andreducedαS-inducedcellulartoxicity.Inaddition,Rab8?theDrosophilaorthologofRab8a?amelioratedαS-oligomerspecificlocomotorimpairmentandneuronlossinfruitflies.InsupportofthepathogenicrelevanceoftheαS?Rab8ainteraction,phosphorylationofαSatS129enhancedbindingtoRab8a,increasedformationofinsolubleαSaggregatesandreducedcellulartoxicity.Ourstudyprovidesnovelmechanisticinsightsintothein-terplayoftheGTPaseRab8aandαScytotoxicity,
