Abstract
Alpha-synuclein is implicated in several neurodegenerative disorders, such as Parkinson's disease and multiple system atrophy, yet its functions remain obscure. When expressed in yeast, alpha-synuclein associated with the plasma membrane in a highly selective manner, before forming cytoplasmic inclusions through a concentration-dependent, nucleated process. Alpha-synuclein inhibited phospholipase D, induced lipid droplet accumulation, and affected vesicle trafficking. This readily manipulable system provides an opportunity to dissect the molecular pathways underlying normal alpha-synuclein biology and the pathogenic consequences of its misfolding.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Cell Division
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Cell Membrane / metabolism
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Cytoplasm / metabolism
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Endocytosis
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Fluorescent Dyes / metabolism
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Inclusion Bodies / metabolism
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Intracellular Membranes / metabolism
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Lipid Metabolism
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / metabolism*
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Nuclear Proteins / metabolism
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Phospholipase D / antagonists & inhibitors
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Phospholipase D / metabolism
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Point Mutation
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Protein Folding
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Pyridinium Compounds / metabolism
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Quaternary Ammonium Compounds / metabolism
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Recombinant Fusion Proteins / metabolism
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / growth & development
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae / physiology
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Synucleins
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Ubiquitin / metabolism
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Vacuoles / metabolism
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alpha-Synuclein
Substances
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FM 4-64
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Fluorescent Dyes
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Nerve Tissue Proteins
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Nuclear Proteins
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Pyridinium Compounds
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Quaternary Ammonium Compounds
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Recombinant Fusion Proteins
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Synucleins
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Ubiquitin
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alpha-Synuclein
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Phospholipase D