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 journalArticle

20 Citations (Scopus)

Abstract

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
Volume26
Issue number12
DOIs
Publication statusPublished - Jun 20 2007

Fingerprint

Calpain
Endocytosis
Synaptic Vesicles
Dynamin I
Electric Stimulation
Dynamins
Phosphorylation
Kainic Acid
Transferrin
Liposomes
Copolymerization
amphiphysin
Potassium
Seizures
Peptide Hydrolases
Proteins

Keywords

  • Amphiphysin
  • Calpain
  • Endocytosis
  • Hyperexcitation
  • Seizure

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Truncations of amphiphysin I by calpain inhibit vesicle endocytosis during neural hyperexcitation. / Wu, Yumei; Liang, Shuang; Oda, Yoshiya; Ohmori, Iori; Nishiki, Tei-ichi; Takei, Kohji; Matsui, Hideki; Tomizawa, Kazuhito.

In: EMBO Journal, Vol. 26, No. 12, 20.06.2007, p. 2981-2990.

Research output: Contribution to journalArticle

Wu, Yumei ; Liang, Shuang ; Oda, Yoshiya ; Ohmori, Iori ; Nishiki, Tei-ichi ; Takei, Kohji ; Matsui, Hideki ; Tomizawa, Kazuhito. / Truncations of amphiphysin I by calpain inhibit vesicle endocytosis during neural hyperexcitation. In: EMBO Journal. 2007 ; Vol. 26, No. 12. pp. 2981-2990.
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