title: Yeast cells provide insight into alpha-synuclein biology and pathobiology.
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.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Tiago Fleming
authors.initials: TF
authors.lastname: Outeiro
authors.forename: Susan
authors.initials: S
authors.lastname: Lindquist
mesh_terms: D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004705:Endocytosis; D005456:Fluorescent Dyes / Q000378:metabolism; D002479:Inclusion Bodies / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D050356:Lipid Metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000378:metabolism; D017354:Point Mutation; D017510:Protein Folding; D011726:Pyridinium Compounds / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D051843:Synucleins; D025801:Ubiquitin / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism; D051844:alpha-Synuclein
chemical_list: C092350:FM 4-64; D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011726:Pyridinium Compounds; D000644:Quaternary Ammonium Compounds; D011993:Recombinant Fusion Proteins; D051843:Synucleins; D025801:Ubiquitin; D051844:alpha-Synuclein; D010739:Phospholipase D