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Truncations of amphiphysin I by calpain inhibit vesicle endocytosis during neural hyperexcitation
Author(s) -
Wu Yumei,
Liang Shuang,
Oda Yoshiya,
Ohmori Iori,
Nishiki Teiichi,
Takei Kohji,
Matsui Hideki,
Tomizawa Kazuhito
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601741
Subject(s) - amphiphysin , endocytosis , dynamin , endocytic cycle , synaptic vesicle , biology , microbiology and biotechnology , calpain , bulk endocytosis , clathrin , neurotransmission , vesicle , synaptic vesicle recycling , biochemistry , receptor , membrane , enzyme
Under normal physiological conditions, synaptic vesicle endocytosis is regulated by phosphorylation and Ca 2+ ‐dependent dephosphorylation of endocytic proteins such as amphiphysin and dynamin. To investigate the regulatory mechanisms that may occur under the conditions of excessive presynaptic Ca 2+ 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.