title: Truncations of amphiphysin I by calpain inhibit vesicle endocytosis during neural hyperexcitation.
abstract: 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.
authors.affiliation: Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikata-cho 2-5-1, Okayama 700-8558, Japan.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Wu
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Oda
authors.forename: Iori
authors.initials: I
authors.lastname: Ohmori
authors.forename: Tei-ichi
authors.initials: T
authors.lastname: Nishiki
authors.forename: Kohji
authors.initials: K
authors.lastname: Takei
authors.forename: Hideki
authors.initials: H
authors.lastname: Matsui
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tomizawa
mesh_terms: D000818:Animals; D002154:Calpain / Q000502:physiology*; D034284:Dynamin I / Q000378:metabolism; D004705:Endocytosis; D006624:Hippocampus / Q000378:metabolism; D006868:Hydrolysis; D008081:Liposomes; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D011188:Potassium / Q000378:metabolism
chemical_list: D008081:Liposomes; D009419:Nerve Tissue Proteins; C075637:amphiphysin; D002154:Calpain; D034284:Dynamin I; D011188:Potassium