Phosphorylation at Ser-129 but Not the Phosphomimics S129E/D Inhibits the Fibrillation of -Synuclein*
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چکیده
From the Laboratory of Molecular Neurobiology and Neuroproteomics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne, CH-1015 Lausanne, Switzerland, Department of Biochemistry and Program in Structural Biology, Weill Cornell Medical College, New York, New York 10021, Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Deutsche Forschungsgemeinschaft Research Center for the Molecular Physiology of the Brain, 37077 Göttingen, Germany, Instituto de Biologı́a Molecular y Celular de Rosario, Consejo Nacional de Investigaciones Cientı́ficas y Técnicas, Universidad Nacional de Rosario, Suipacha 531, S2002LRK Rosario, Argentina, and **Harvard Center for Neurodegeneration and Repair, Center for Neurologic Diseases, Brigham and Women’s Hospital and Department of Neurology, Harvard Medical School, Cambridge, Massachusetts 02139
منابع مشابه
Phosphorylation at Ser-129 but not the phosphomimics S129E/D inhibits the fibrillation of alpha-synuclein.
alpha-Synuclein (alpha-syn) phosphorylation at serine 129 is characteristic of Parkinson disease (PD) and related alpha-synulceinopathies. However, whether phosphorylation promotes or inhibits alpha-syn aggregation and neurotoxicity in vivo remains unknown. This understanding is critical for elucidating the role of alpha-syn in the pathogenesis of PD and for development of therapeutic strategie...
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Several neurological diseases, including Parkinson disease and dementia with Lewy bodies, are characterized by the accumulation of alpha-synuclein phosphorylated at Ser-129 (p-Ser-129). The kinase or kinases responsible for this phosphorylation have been the subject of intense investigation. Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a...
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Mutations and copy number variation in the SNCA gene encoding the neuronal protein -synuclein have been linked to familial Parkinson disease (Thomas, B., and Beal, M. F. (2007) Parkinson’s disease. Hum. Mol. Genet. 16, R183– R194). The carboxyl terminus of -synuclein can be phosphorylated at tyrosine 125 and serine 129, although only a small fraction of the protein is phosphorylated under norma...
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Although α-synuclein (α-syn) phosphorylation has been considered as a hallmark of sporadic and familial Parkinson disease (PD), little is known about the effect of PD-linked mutations on α-syn phosphorylation. In this study, we investigated the effects of the A30P, E46K, and A53T PD-linked mutations on α-syn phosphorylation at residues Ser-87 and Ser-129. Although the A30P and A53T mutants slig...
متن کاملSerine 129 Phosphorylation Reduces the Ability of α-Synuclein to Regulate Tyrosine Hydroxylase and Protein Phosphatase 2A in Vitro and in Vivo*
Alpha-synuclein (a-Syn), a protein implicated in Parkinson disease, contributes significantly to dopamine metabolism. a-Syn binding inhibits the activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. Phosphorylation of TH stimulates its activity, an effect that is reversed by protein phosphatase 2A (PP2A). In cells, a-Syn overexpression activates PP2A. Here ...
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تاریخ انتشار 2008