Truncations of amphiphysin I by calpain inhibit vesicle endocytosis during neural hyperexcitation

Yumei Wu, Shuang Liang, Yoshiya Oda, Iori Ohmori, Tei-ichi Nishiki, Kohji Takei, Hideki Matsui, Kazuhito Tomizawa

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2981-2990
Number of pages10
JournalEMBO Journal
Issue number12
Publication statusPublished - Jun 20 2007


  • Amphiphysin
  • Calpain
  • Endocytosis
  • Hyperexcitation
  • Seizure

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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