Effect of Trehalose on the Properties of Mutant γPKC, Which Causes Spinocerebellar Ataxia Type 14, in Neuronal Cell Lines and Cultured Purkinje Cells

The Journal of Biological Chemistry 285 巻 43 号 33252-33264 頁 2010-08-12 発行
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タイトル ( eng )
Effect of Trehalose on the Properties of Mutant γPKC, Which Causes Spinocerebellar Ataxia Type 14, in Neuronal Cell Lines and Cultured Purkinje Cells
作成者
Seki Takahiro
Abe-Seki Nana
Kikawada Takahiro
Takahashi Hideyuki
Adachi Naoko
Saito Naoaki
収録物名
The Journal of Biological Chemistry
285
43
開始ページ 33252
終了ページ 33264
抄録
Several missense mutations in the protein kinase C gamma (gamma PKC) gene have been found to cause spinocerebellar ataxia type 14 (SCA14), an autosomal dominant neurodegenerative disease. We previously demonstrated that the mutant gamma PKC found in SCA14 is susceptible to aggregation, which induces apoptotic cell death. The disaccharide trehalose has been reported to inhibit aggregate formation and to alleviate symptoms in cellular and animal models of Huntington disease, Alzheimer disease, and prion disease. Here, we show that trehalose can be incorporated into SH-SY5Y cells and reduces the aggregation of mutant gamma PKC-GFP, thereby inhibiting apoptotic cell death in SH-SY5Y cells and primary cultured Purkinje cells (PCs). Trehalose acts by directly stabilizing the conformation of mutant gamma PKC without affecting protein turnover. Trehalose was also found to alleviate the improper development of dendrites in PCs expressing mutant gamma PKC-GFP without aggregates but not in PCs with aggregates. In PCs without aggregates, trehalose improves the mobility and translocation of mutant gamma PKC-GFP, probably by inhibiting oligomerization and thereby alleviating the improper development of dendrites. These results suggest that trehalose counteracts various cellular dysfunctions that are triggered by mutant gamma PKC in both neuronal cell lines and primary cultured PCs by inhibiting oligomerization and aggregation of mutant gamma PKC.
NDC分類
医学 [ 490 ]
言語
英語
資源タイプ 学術雑誌論文
出版者
American Society for Biochemistry and Molecular Biology Inc
発行日 2010-08-12
権利情報
Copyright (c) 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
出版タイプ Author’s Original(十分な品質であるとして、著者から正式な査読に提出される版)
アクセス権 オープンアクセス
収録物識別子
[ISSN] 0021-9258
[DOI] 10.1074/jbc.M110.146704
[NCID] AA00251083
[DOI] http://dx.doi.org/10.1074/jbc.M110.146704