Rapsyn Interaction with Calpain Stabilizes AChR Clusters at the Neuromuscular Junction

Fei Chen, Lei Qian, Zhi Hua Yang, Ying Huang, Shyuan T. Ngo, Nan Jie Ruan, Jia Wang, Claudio Schneider, Peter G. Noakes, Yu Qiang Ding, Lin Mei, Zhen Ge Luo

Research output: Contribution to journalArticle

73 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)247-260
Number of pages14
JournalNeuron
Volume55
Issue number2
DOIs
StatePublished - Jul 19 2007

Keywords

  • CELLBIO
  • MOLNEURO
  • SIGNALING

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Chen, F., Qian, L., Yang, Z. H., Huang, Y., Ngo, S. T., Ruan, N. J., Wang, J., Schneider, C., Noakes, P. G., Ding, Y. Q., Mei, L., & Luo, Z. G. (2007). Rapsyn Interaction with Calpain Stabilizes AChR Clusters at the Neuromuscular Junction. Neuron, 55(2), 247-260. https://doi.org/10.1016/j.neuron.2007.06.031