| Literature DB >> 18634833 |
Piotr Zabrocki1, Ilse Bastiaens, Charlotte Delay, Tine Bammens, Ruben Ghillebert, Klaartje Pellens, Claudio De Virgilio, Fred Van Leuven, Joris Winderickx.
Abstract
Parkinson's disease is a neurodegenerative disorder characterized by the formation of Lewy bodies containing aggregated alpha-synuclein. We used a yeast model to screen for deletion mutants with mislocalization and enhanced inclusion formation of alpha-synuclein. Many of the mutants were affected in functions related to vesicular traffic but especially mutants in endocytosis and vacuolar degradation combined inclusion formation with enhanced alpha-synuclein-mediated toxicity. The screening also allowed for identification of casein kinases responsible for alpha-synuclein phosphorylation at the plasma membrane as well as transacetylases that modulate the alpha-synuclein membrane interaction. In addition, alpha-synuclein was found to associate with lipid rafts, a phenomenon dependent on the ergosterol content. Together, our data suggest that toxicity of alpha-synuclein in yeast is at least in part associated with endocytosis of the protein, vesicular recycling back to the plasma membrane and vacuolar fusion defects, each contributing to the obstruction of different vesicular trafficking routes.Entities:
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Year: 2008 PMID： 18634833 DOI： 10.1016/j.bbamcr.2008.06.010
Source DB: PubMed Journal: Biochim Biophys Acta ISSN： 0006-3002