Activity-dependent cleavage of brain glutamic acid decarboxylase 65 by calpain

Jianning Wei, Chun Hua Lin, Heng Wu, Ying Jin, Yi Hsuan Lee, Jang Yen Wu

研究成果: 雜誌貢獻文章

15 引文 斯高帕斯(Scopus)

摘要

Previously, we reported that L-glutamic acid decarboxylase isoform 65 (GAD65) could be cleaved in vitro to release a stable truncated form which lacks amino acid 1-69 from the N-terminus, GAD65(Δ1-69). However, whether such a truncated form is also present under certain physiological conditions remains elusive. In the present study, we showed that, upon sustained neuronal stimulation, GAD65 could be cleaved into a truncated form in a rat synaptosomal preparation. This truncated form had similar electrophoretic mobility to purified recombinant human GAD65(Δ1-69). Furthermore, we demonstrated that this conversion was calcium dependent. Calcium-chelating reagents such as EDTA and 1,2-bis-(o-aminphenoxy)-ethane-N,N,N′,N′-tetra-acetic acid tetra-acetoxy-methyl ester prevented the cleavage of GAD65. In addition, our data suggested that calpain, a calcium-dependent cysteine protease, is activated upon neuronal stimulation and could be responsible for the conversion of full-length GAD65 to truncated GAD65 in the brain. Moreover, calpain inhibitors such as calpain inhibitor I or calpastatin could block the cleavage. Results of our in vitro cleavage assay using purified calpain and immunopurified rat GAD65 also supported the idea that GAD65 could be directly cleaved by calpain.
原文英語
頁(從 - 到)1688-1695
頁數8
期刊Journal of Neurochemistry
98
發行號5
DOIs
出版狀態已發佈 - 九月 2006

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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