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PMID: 14657500 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Yeast cells provide insight into alpha-synuclein biology and pathobiology.

Science (New York, N.Y.) ·Vol. 302 ·No. 5651 ·2003-12-05 ·Pages 1772-5

Outeiro TF, Lindquist S

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.

MeSH Terms
Cell Division Cell Membrane/metabolism Cytoplasm/metabolism Endocytosis Fluorescent Dyes/metabolism Inclusion Bodies/metabolism Intracellular Membranes/metabolism Lipid Metabolism Nerve Tissue Proteins/chemistry,genetics,metabolism Nuclear Proteins/metabolism Phospholipase D/antagonists & inhibitors,metabolism Point Mutation Protein Folding Pyridinium Compounds/metabolism Quaternary Ammonium Compounds/metabolism Recombinant Fusion Proteins/metabolism Saccharomyces cerevisiae/genetics,growth & development,metabolism,physiology Synucleins Ubiquitin/metabolism Vacuoles/metabolism alpha-Synuclein
Chemicals
FM 4-64 Fluorescent Dyes Nerve Tissue Proteins Nuclear Proteins Pyridinium Compounds Quaternary Ammonium Compounds Recombinant Fusion Proteins Synucleins Ubiquitin alpha-Synuclein Phospholipase D
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Outeiro Tiago Fleming
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Lindquist Susan
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1090439
Published
2003-12-05
Pages
1772-5
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC1780172
Subset
IM
Grants
NINDS NIH HHS · NS044829-01 · United States
External Links
PubMed source DOI: 10.1126/science.1090439 PMC Full Text View journal details
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