Role of μ-calpain in proteolytic cleavage of brain l-glutamic acid decarboxylase

Di Sha, Ying Jin, Heng Wu, Jianning Wei, Chun Hua Lin, Yi Hsuan Lee, Chandana Buddhala, Shafi Kuchay, Athar H. Chishti, Jang Yen Wu*

*此作品的通信作者

研究成果: Article同行評審

17 引文 斯高帕斯(Scopus)

摘要

Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme for γ-aminobutyric acid (GABA) biosynthesis. Previously, we reported the presence of truncated forms of GAD in vivo and in vitro. In addition, an unidentified endogenous protease responsible for proteolytic cleavage of full-length GAD (fGAD) to its truncated form (tGAD) was also observed. In this communication, we report that μ-calpain is a good candidate for conversion of fGAD67 to tGAD67. This conclusion is based on the following observations: 1. purified recombinant GAD67 is cleaved by μ-calpain at specific sites; 2. in brain synaptosomal preparation, GAD67 is cleaved to its truncated form by an endogenous protease which is inhibited by specific calpain inhibitors; 3. in μ-calpain knockout mice, the level of tGAD in the brain is greatly reduced compared with the wild type; 4. when μ-calpain gene is silenced by siRNA, the level of tGAD is also markedly reduced compared to the control group; and 5. μ-calpain is activated by neuronal stimulation and Ca2+-influx. The physiological significance of calpain in regulation of GABA synthesis and GABAergic neurotransmission is also discussed.

原文English
頁(從 - 到)9-18
頁數10
期刊Brain Research
1207
DOIs
出版狀態Published - 1 5月 2008

指紋

深入研究「Role of μ-calpain in proteolytic cleavage of brain l-glutamic acid decarboxylase」主題。共同形成了獨特的指紋。

引用此