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Title: The small GTPase Rab11 co-localizes with α-synuclein in intracellular inclusions and modulates its aggregation, secretion and toxicity
Authors: Chutna, O.
Gonçalves, S.
Villar-Piqué, A.
Guerreiro, P.
Marijanovic, Z.
Mendes, T.
Ramalho, J.
Emmanouilidou, E.
Ventura, S.
Klucken, J.
Barral, D. C.
Giorgini, Flaviano
Vekrellis, K.
Outeiro, T. F.
First Published: 4-Aug-2014
Publisher: Oxford University Press (OUP)
Citation: Human Molecular Genetics, 2014, 23 (25), pp. 6732-6745
Abstract: Alpha-synuclein (aSyn) misfolding and aggregation are pathological features common to several neurodegenerative diseases, including Parkinson's disease (PD). Mounting evidence suggests that aSyn can be secreted and transferred from cell to cell, participating in the propagation and spreading of pathological events. Rab11, a small GTPase, is an important regulator in both endocytic and secretory pathways. Here, we show that Rab11 is involved in regulating aSyn secretion. Rab11 knockdown or overexpression of either Rab11a wild-type (Rab11a WT) or Rab11a GDP-bound mutant (Rab11a S25N) increased secretion of aSyn. Furthermore, we demonstrate that Rab11 interacts with aSyn and is present in intracellular inclusions together with aSyn. Moreover, Rab11 reduces aSyn aggregation and toxicity. Our results suggest that Rab11 is involved in modulating the processes of aSyn secretion and aggregation, both of which are important mechanisms in the progression of aSyn pathology in PD and other synucleinopathies.
DOI Link: 10.1093/hmg/ddu391
ISSN: 0964-6906
eISSN: 1460-2083
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: The file associated with this record is distributed under the Creative Commons “Attribution Non-Commercial No Derivatives” licence, further details of which can be found via the following link:
Appears in Collections:Published Articles, Dept. of Genetics

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