Novel insights into alpha syynuclein intracellular dynamics

Abstract

Event Abstract Back to Event Novel insights into alpha syynuclein intracellular dynamics Susana Goncalves1* and Tiago Fleming-Outeiro1 1 Faculdade de Medicina da Universidade de Lisboa, Instituto de Medicina Molecular, Cell and Molecular Neuroscience Unit, Instituto de Fisiologia, Portugal Alpha Synuclein (asyn) is a pre-synaptic protein implicated in several neurodegenerative disorders such as Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). The pathological hallmark among these disorders is the accumulation of “misfolded” asyn in inclusions known as Lewy bodies (LBs). Most asyn in LBs is phosphorylated at Ser129 but the role of this post-translational modification is still unclear. The aggregation process is thought to culminate with the disruption of several essential cellular functions and consequent cell death. Although asyn has been implicated in synaptic transmission and dopamine transport, its function remains elusive. Moreover, its function may vary with the intracellular location and the stage of neuronal differentiation. To gain insight into the biology of asyn in the cell we generated asyn-fusions with a photoactivable green fluorescent protein (PAGFP), which enabled us to study its subcellular dynamics in living cells using confocal microscopy. We compared the behavior of wild type and the three mutant forms of asyn that are found in PD patients, A30P, E46K and A53T, to assess the effect of familial mutations. We found that asyn shuttles between the nucleus and cytoplasm of mammalian cells at rates which vary depending on the cell type used. We also found that the three mutant foms of asyn alter the rate at which asyn distributes throughout the cell. In order to determine the role of asyn phosphorylation on its dynamics and aggregation, we are using mutants which mimic (S129D) or abolish (S129A) phosphorylation. Taken together, these results will provide novel insights into the molecular determinants of asyn subcellular distribution and bear important implications for further development of therapeutic approaches. Conference: 11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009. Presentation Type: Poster Presentation Topic: Neurodegenerative Disorders Citation: Goncalves S and Fleming-Outeiro T (2009). Novel insights into alpha syynuclein intracellular dynamics. Front. Neurosci. Conference Abstract: 11th Meeting of the Portuguese Society for Neuroscience. doi: 10.3389/conf.neuro.01.2009.11.033 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: 06 Aug 2009; Published Online: 06 Aug 2009. * Correspondence: Susana Goncalves, Faculdade de Medicina da Universidade de Lisboa, Instituto de Medicina Molecular, Cell and Molecular Neuroscience Unit, Instituto de Fisiologia, Lisboa, Portugal, sabgoncalves@gmail.com 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 Susana Goncalves Tiago Fleming-Outeiro Google Susana Goncalves Tiago Fleming-Outeiro Google Scholar Susana Goncalves Tiago Fleming-Outeiro PubMed Susana Goncalves Tiago Fleming-Outeiro 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.