Phosphorylation, lipid raft interaction and traffic of α-synuclein in a yeast model for Parkinson
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Zabrocki, Piotr
Laboratory of Functional Biology, Heverlee, Belgium
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Bastiaens, Ilse
Laboratory of Functional Biology, Heverlee, Belgium
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Delay, Charlotte
Laboratory of Functional Biology, Heverlee, Belgium
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Bammens, Tine
Laboratory of Functional Biology, Heverlee, Belgium
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Ghillebert, Ruben
Laboratory of Functional Biology, Heverlee, Belgium
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Pellens, Klaartje
Laboratory of Functional Biology, Heverlee, Belgium
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De Virgilio, Claudio
Department of Medicine, Division of Biochemistry, University of Fribourg, Switzerland
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Leuven, Fred Van
Experimental Genetics Group, Katholieke Universiteit Leuven, Belgium
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Winderickx, Joris
Laboratory of Functional Biology, Heverlee, Belgium
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Published in:
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. - 2008, vol. 1783, no. 10, p. 1767-1780
English
Parkinson's disease is a neurodegenerative disorder characterized by the formation of Lewy bodies containing aggregated α-synuclein. We used a yeast model to screen for deletion mutants with mislocalization and enhanced inclusion formation of α-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 α-synuclein-mediated toxicity. The screening also allowed for identification of casein kinases responsible for α-synuclein phosphorylation at the plasma membrane as well as transacetylases that modulate the α-synuclein membrane interaction. In addition, α-synuclein was found to associate with lipid rafts, a phenomenon dependent on the ergosterol content. Together, our data suggest that toxicity of α-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.
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Faculty
- Faculté des sciences et de médecine
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Department
- Département de Biologie
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Language
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Classification
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Biological sciences
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License
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License undefined
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Identifiers
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Persistent URL
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https://folia.unifr.ch/unifr/documents/301424
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