Clearance and phosphorylation of alpha-synuclein are inhibited in methionine sulfoxide reductase a null yeast cells.
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.
Oien
Derek B
DB
Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS 66045, USA.
Shinogle
Heather E
HE
Moore
David S
DS
Moskovitz
Jackob
J
D000595:Amino Acid Sequence / Q000502:physiology; D047390:Casein Kinase II / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D055786:Gene Knockout Techniques; D008715:Methionine / Q000031:analogs & derivatives / Q000378:metabolism*; D051150:Methionine Sulfoxide Reductases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009454:Neurofibrils / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
D051844:alpha-Synuclein; D008715:Methionine; D051150:Methionine Sulfoxide Reductases; D047390:Casein Kinase II; C013111:methionine sulfoxide