N-terminal region of alpha-synuclein is essential for the fatty acid-induced oligomerization of the molecules |
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Authors: | Karube Hiroki Sakamoto Masahiro Arawaka Shigeki Hara Susumu Sato Hiroyasu Ren Chang-Hong Goto Saori Koyama Shingo Wada Manabu Kawanami Toru Kurita Keiji Kato Takeo |
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Affiliation: | Department of Neurology, Yamagata University, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan. |
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Abstract: | Exposure of alpha-synuclein (alphaS), a major component of Lewy bodies in Parkinson's disease, to polyunsaturated fatty acids (PUFAs) triggers the formation of soluble alphaS oligomers. Here, we demonstrate that PUFA binds recombinant alphaS protein through its N-terminal region (residues 2-60). In HEK293 cells, alphaS mutants lacking the N-terminal region failed to form oligomers in the presence of PUFA. The PUFA-induced alphaS oligomerization was accelerated by C-terminal truncation or Ser129 phosphorylation of alphaS; however, this effect was abolished by deletion of the N-terminus. The results indicate that the N-terminus of alphaS is essential for the PUFA-induced alphaS oligomerization. |
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