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Casein kinase 2 is the major enzyme in brain that phosphorylates Ser129 of human alpha-synuclein: Implication for alpha-synucleinopathies |
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| Authors: | Ishii Aasami Nonaka Takashi Taniguchi Sayuri Saito Taro Arai Tetsuaki Mann David Iwatsubo Takeshi Hisanaga Shin-Ichi Goedert Michel Hasegawa Masato |
| Institution: | a Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan b Molecular Neuroscience Laboratory, Graduate School of Science, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji-shi, Tokyo 192-0397, Japan c Department of Psychogeriatrics, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan d Greater Manchester Neurosciences Centre, University of Manchester, Hope Hospital, Salford M6 8HD, UK e Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan f Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK |
| Abstract: | In Lewy body diseases and multiple system atrophy, α-synuclein is hyperphosphorylated at Ser129, suggesting a role in pathogenesis. Here, we report purification of the protein kinase in rat brain that phosphorylates Ser129 and its identification as casein kinase-2 (CK2). We show that most of the activity can be inhibited by heparin, an inhibitor of CK2. Phosphorylated Ser129 was detected in primary cultured neurons and inhibited by CK2 inhibitors. In some cases of Lewy body disease, CK2-like immunoreactivity was recovered in the sarkosyl-insoluble fraction, which was enriched in phosphorylated α-synuclein. Taken together, these findings suggest that CK2 may be involved in the hyperphosphorylation of α-synuclein in α-synucleinopathies. |
| Keywords: | Aggregation Parkinson&rsquo s disease Lewy body Heparin Mutation CK2 |
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