Event Abstract Back to Event Alpha-synuclein and rab3a interactions: Effects on membrane binding Robert H. Chen1, 2*, N. Visanji2, S. Wislet-Gendebien2, G. Zhang2, Howard T. Mount1, 2, 3 and A. Tandon2, 3 1 University of Toronto, Department of Physiology, Canada 2 University of Toronto, Centre for Research in Neurodegenerative Diseases, Canada 3 University of Toronto, Institute of Medical Science, Canada The development of intracellular inclusions known as Lewy bodies is a histopathological hallmark of Parkinson’s disease (PD). The major component of these inclusions is α-synuclein, a protein that is predominantly localized to the pre-synaptic terminals of neurons. α-Synuclein is known to alternate between membrane-bound and cytosolic compartments. The dissociation of α-synuclein from vesicular membranes is mediated by brain cytosolic proteins and may play a role in the formation of neurotoxic fibrils under pathological conditions. Previous work from our lab suggests that the small GTPase rab3a is involved in the binding of α-synuclein to synaptic membranes. In this study, we show that rab3a can be co-immunoprecipitated with α-synuclein in synaptosomes generated from murine brains and that this interaction appears to occur preferentially on vesicle membranes. Furthermore, we show that upon depolarization, the over-expression of a predominately GTP-bound rab3a mutant in SH-SY5Y human neuroblastoma cells causes a reduction of soluble compartment α-synuclein as compared to over-expression of wild-type rab3a. This effect is independent of the distribution of mutant rab3a between the membrane and soluble compartments. We found a similar effect on α-synuclein compartmentalization upon disruption of the complex that chaperones rab3a off of synaptic membranes in SH-SY5Y cells. Our results suggest that α-synuclein membrane binding is mediated by both the localization and GTP-binding status of membrane-bound rab3a. These results further the understanding of α-synuclein compartmentalization dynamics under non-pathological conditions. This work was supported by CIHR grant to AT. Conference: B.R.A.I.N. platform in Physiology poster day 2009, Toronto, ON, Canada, 16 Dec - 16 Dec, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Chen RH, Visanji N, Wislet-Gendebien S, Zhang G, Mount HT and Tandon A (2009). Alpha-synuclein and rab3a interactions: Effects on membrane binding. Front. Neurosci. Conference Abstract: B.R.A.I.N. platform in Physiology poster day 2009. doi: 10.3389/conf.neuro.03.2009.17.006 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 16 Dec 2009; Published Online: 16 Dec 2009. * Correspondence: Robert H Chen, University of Toronto, Department of Physiology, Toronto, Canada, r.chen@mail.utoronto.ca Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Robert H Chen N. Visanji S. Wislet-Gendebien G. Zhang Howard T Mount A. Tandon Google Robert H Chen N. Visanji S. Wislet-Gendebien G. Zhang Howard T Mount A. Tandon Google Scholar Robert H Chen N. Visanji S. Wislet-Gendebien G. Zhang Howard T Mount A. Tandon PubMed Robert H Chen N. Visanji S. Wislet-Gendebien G. Zhang Howard T Mount A. Tandon Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.