Please use this identifier to cite or link to this item:
Title: Rab11 modulates α-synuclein-mediated defects in synaptic transmission and behaviour
Authors: Breda, Carlo
Nugent, Marie L.
Estranero, Jasper G.
Kyriacou, Charalambos P.
Outeiro, Tiago F.
Steinert, Joern R.
Giorgini, Flaviano
First Published: 9-Oct-2014
Publisher: Oxford University Press
Citation: Human Molecular Genetics, 2015, 24 (4), pp. 1077-1091
Abstract: A central pathological hallmark of Parkinson's disease (PD) is the presence of proteinaceous depositions known as Lewy bodies, which consist largely of the protein α-synuclein (aSyn). Mutations, multiplications and polymorphisms in the gene encoding aSyn are associated with familial forms of PD and susceptibility to idiopathic PD. Alterations in aSyn impair neuronal vesicle formation/transport, and likely contribute to PD pathogenesis by neuronal dysfunction and degeneration. aSyn is functionally associated with several Rab family GTPases, which perform various roles in vesicle trafficking. Here, we explore the role of the endosomal recycling factor Rab11 in the pathogenesis of PD using Drosophila models of aSyn toxicity. We find that aSyn induces synaptic potentiation at the larval neuromuscular junction by increasing synaptic vesicle (SV) size, and that these alterations are reversed by Rab11 overexpression. Furthermore, Rab11 decreases aSyn aggregation and ameliorates several aSyn-dependent phenotypes in both larvae and adult fruit flies, including locomotor activity, degeneration of dopaminergic neurons and shortened lifespan. This work emphasizes the importance of Rab11 in the modulation of SV size and consequent enhancement of synaptic function. Our results suggest that targeting Rab11 activity could have a therapeutic value in PD.
DOI Link: 10.1093/hmg/ddu521
ISSN: 0964-6906
eISSN: 1460-2083
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2014. This is an open-access article distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Genetics

Files in This Item:
File Description SizeFormat 
Hum. Mol. Genet.-2015-Breda-1077-91.pdfPublished (publisher PDF)1.29 MBAdobe PDFView/Open

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.