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Title: Rapsyn interaction with calpain stabilizes AChR clusters at the neuromuscular junction
Author: Chen, Fei ; Qian, Lei ; Yang, Zhi-Hua ; Huang, Ying ; Ngo, Shyuan T. ; Ruan, Nan-Jie ; Wang, Jia ; Schneider, Claudio ; Noakes, Peter G. ; Ding, Yu-Qiang ; Mei, Lin ; null(罗振革)
Source: NEURON
Issued Date: 2007
Volume: 55, Issue:2, Pages:247-260
Keyword: CYCLIN-DEPENDENT KINASE-5 ; ACETYLCHOLINE-RECEPTOR CLUSTERS ; ALTERNATIVELY SPLICED ISOFORMS ; SYNAPSE FORMATION ; CDK5 ACTIVITY ; RAT MYOTUBES ; NULL MICE ; AGRIN ; P25 ; PROTEIN
Subject: Neurosciences & Neurology
Corresponding Author: Luo, ZG (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, 320 Yue Yang Rd, Shanghai 200031, Peoples R China,zgluo@ion.ac.cn
English Abstract: Agrin induces, whereas acetylcholine (ACh) disperses, ACh receptor (AChR) clusters during neuromuscular synaptogenesis. Such counteractive interaction leads to eventual dispersal of nonsynaptic AChR-rich sites and formation of receptor clusters at the postjunctional membrane. However, the underlying mechanisms are not well understood. Here we show that calpain, a calcium-dependent protease, is activated by the cholinergic stimulation and is required for induced dispersion of AChR clusters. Interestingly, the AChR-associated protein rapsyn interacted with calpain in an agrin-dependent manner, and this interaction inhibited the protease activity of calpain. Disrupting the endogenous rapsyn/calpain interaction enhanced CCh-induced dispersion of AChR clusters. Moreover, the loss of AChR clusters in agrin mutant mice was partially rescued by the inhibition of calpain via overexpressing calpastatin, an endogenous calpain inhibitor, or injecting calpeptin, a cell-permeable calpain inhibitor. These results demonstrate that calpain participates in ACh-induced dispersion of AChR clusters, and rapsyn stabilizes AChR clusters by suppressing calpain activity.
Indexed Type: sci
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1758
Appears in Collections:神经所(总)_期刊论文
突触信号研究组_期刊论文

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Chen, Fei; Qian, Lei; Yang, Zhi-Hua; Huang, Ying; Ngo, Shyuan T.; Ruan, Nan-Jie; Wang, Jia; Schneider, Claudio; Noakes, Peter G.; Ding, Yu-Qiang; Mei, Lin; Luo, Zhen-Ge.Rapsyn interaction with calpain stabilizes AChR clusters at the neuromuscular junction,NEURON,2007,55(2):247-260
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