Enzymatic Activity of the Scaffold Protein Rapsyn for Synapse Formation

Lei Li, Yu Cao, Haitao Wu, Xinchun Ye, Zhihui Zhu, Guanglin Xing, Chengyong Shen, Arnab Barik, Bin Zhang, Xiaoling Xie, Wenbo Zhi, Lin Gan, Huabo Su, Wen Cheng Xiong, Lin Mei

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28 Scopus citations

Abstract

Neurotransmission is ensured by a high concentration of neurotransmitter receptors at the postsynaptic membrane. This is mediated by scaffold proteins that bridge the receptors with cytoskeleton. One such protein is rapsyn (receptor-associated protein at synapse), which is essential for acetylcholine receptor (AChR) clustering and NMJ (neuromuscular junction) formation. We show that the RING domain of rapsyn contains E3 ligase activity. Mutation of the RING domain that abolishes the enzyme activity inhibits rapsyn- as well as agrin-induced AChR clustering in heterologous and muscle cells. Further biological and genetic studies support a working model where rapsyn, a classic scaffold protein, serves as an E3 ligase to induce AChR clustering and NMJ formation, possibly by regulation of AChR neddylation. This study identifies a previously unappreciated enzymatic function of rapsyn and a role of neddylation in synapse formation, and reveals a potential target of therapeutic intervention for relevant neurological disorders.

Original languageEnglish (US)
Pages (from-to)1007-1019
Number of pages13
JournalNeuron
Volume92
Issue number5
DOIs
StatePublished - Dec 7 2016

Keywords

  • AChR
  • E3 ligase
  • RING domain
  • neddylation
  • rapsyn

ASJC Scopus subject areas

  • Neuroscience(all)

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    Li, L., Cao, Y., Wu, H., Ye, X., Zhu, Z., Xing, G., Shen, C., Barik, A., Zhang, B., Xie, X., Zhi, W., Gan, L., Su, H., Xiong, W. C., & Mei, L. (2016). Enzymatic Activity of the Scaffold Protein Rapsyn for Synapse Formation. Neuron, 92(5), 1007-1019. https://doi.org/10.1016/j.neuron.2016.10.023