Article

Journal of Molecular Neuroscience

, 39:323

First online:

Clearance and Phosphorylation of Alpha-Synuclein Are Inhibited in Methionine Sulfoxide Reductase A Null Yeast Cells

  • Derek B. OienAffiliated withDepartment of Pharmacology and Toxicology, School of Pharmacy, University of Kansas
  • , Heather E. ShinogleAffiliated withDepartment of Biomedical Services Labs, University of Kansas
  • , David S. MooreAffiliated withDepartment of Biomedical Services Labs, University of Kansas
  • , Jackob MoskovitzAffiliated withDepartment of Pharmacology and Toxicology, School of Pharmacy, University of Kansas Email author 

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Abstract

Aggregated α-synuclein and the point mutations Ala30Pro and Ala53Thr of α-synuclein are associated with Parkinson’s disease. The physiological roles of α-synuclein and methionine oxidation of the α-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 α-synuclein on basic cellular processes, α-synucleins were expressed in msrA null mutant and wild-type yeast cells. Protein degradation was inhibited in the α-synuclein-expressing msrA null mutant cells compared to α-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 α-synuclein phosphorylation in yeast cells and in vitro by casein kinase 2. Thus, a compromised MsrA function combined with α-synuclein overexpression may promote processes leading to synucleinopathies.

Keywords

Oxidative stress Posttranslation modification Neurodegenerative diseases Parkinson’s disease Antioxidants Protein aggregation Yeast Synuclein