2007年6月
Truncations of amphiphysin I by calpain inhibit vesicle endocytosis during neural hyperexcitation
EMBO JOURNAL
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- 巻
- 26
- 号
- 12
- 開始ページ
- 2981
- 終了ページ
- 2990
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1038/sj.emboj.7601741
- 出版者・発行元
- NATURE PUBLISHING GROUP
Under normal physiological conditions, synaptic vesicle endocytosis is regulated by phosphorylation and Ca2+-dependent dephosphorylation of endocytic proteins such as amphiphysin and dynamin. To investigate the regulatory mechanisms that may occur under the conditions of excessive presynaptic Ca2+ influx observed preceding neural hyperexcitation, we examined hippocampal slices following high-potassium or high-frequency electrical stimulation (HFS). In both cases, three truncated forms of amphiphysin I resulted from cleavage by the protease calpain. In vitro, the binding of truncated amphiphysin I to dynamin I and copolymerization into rings with dynamin I were inhibited, but its interaction with liposomes was not affected. Moreover, overexpression of the truncated form of amphiphysin I inhibited endocytosis of transferrin and synaptic vesicles. Inhibiting calpain prevented HFS-induced depression of presynaptic transmission. Finally, calpain-dependent amphiphysin I cleavage attenuated kainate-induced seizures. These results suggest that calpain-dependent cleavage of amphiphysin I inhibits synaptic vesicle endocytosis during neural hyperexcitation and demonstrate a novel post-translational regulation of endocytosis.
- リンク情報
- ID情報
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- DOI : 10.1038/sj.emboj.7601741
- ISSN : 0261-4189
- Web of Science ID : WOS:000248038200015