Clearance and phosphorylation of alpha-synuclein are inhibited in methionine sulfoxide reductase a null yeast cells

J Mol Neurosci. 2009 Nov;39(3):323-32. doi: 10.1007/s12031-009-9274-8. Epub 2009 Aug 4.


Aggregated alpha-synuclein and the point mutations Ala30Pro and Ala53Thr of alpha-synuclein are associated with Parkinson's disease. The physiological roles of alpha-synuclein and methionine oxidation of the alpha-synuclein protein structure and function are not fully understood. Methionine sulfoxide reductase A (MsrA) reduces methionine sulfoxide residues and functions as an antioxidant. To monitor the effect of methionine oxidation to alpha-synuclein on basic cellular processes, alpha-synucleins were expressed in msrA null mutant and wild-type yeast cells. Protein degradation was inhibited in the alpha-synuclein-expressing msrA null mutant cells compared to alpha-synuclein-expressing wild-type cells. Increased inhibition of degradation and elevated accumulations of fibrillated proteins were observed in SynA30P-expressing msrA null mutant cells. Additionally, methionine oxidation inhibited alpha-synuclein phosphorylation in yeast cells and in vitro by casein kinase 2. Thus, a compromised MsrA function combined with alpha-synuclein overexpression may promote processes leading to synucleinopathies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / physiology
  • Casein Kinase II / metabolism
  • Gene Expression Regulation, Enzymologic / genetics
  • Gene Knockout Techniques
  • Methionine / analogs & derivatives
  • Methionine / metabolism*
  • Methionine Sulfoxide Reductases / genetics
  • Methionine Sulfoxide Reductases / metabolism*
  • Mutation / genetics
  • Neurofibrils / genetics
  • Neurofibrils / metabolism
  • Neurofibrils / pathology
  • Oxidation-Reduction
  • Oxidative Phosphorylation
  • Oxidative Stress / genetics*
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Parkinson Disease / physiopathology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Up-Regulation / physiology
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism*


  • alpha-Synuclein
  • Methionine
  • Methionine Sulfoxide Reductases
  • Casein Kinase II
  • methionine sulfoxide