Yeast cells provide insight into alpha-synuclein biology and pathobiology

Science. 2003 Dec 5;302(5651):1772-5. doi: 10.1126/science.1090439.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

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
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Proteins / metabolism
  • Phospholipase D / antagonists & inhibitors
  • Phospholipase D / metabolism
  • Point Mutation
  • Protein Folding
  • Pyridinium Compounds / metabolism
  • Quaternary Ammonium Compounds / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae / physiology
  • Synucleins
  • Ubiquitin / metabolism
  • Vacuoles / metabolism
  • alpha-Synuclein

Substances

  • FM 4-64
  • Fluorescent Dyes
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Pyridinium Compounds
  • Quaternary Ammonium Compounds
  • Recombinant Fusion Proteins
  • Synucleins
  • Ubiquitin
  • alpha-Synuclein
  • Phospholipase D