[SMC] Rapsyn-acetylcholine receptor interactions: structural models inform mechanisms of clustering at the neuromuscular

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Biophys Rev. 2025 Dec 6;17(6):1749-1762. doi: 10.1007/s12551-025-01386-8. eCollection 2025 Dec.

ABSTRACT

Synaptic communication across the neuromuscular junction is mediated by high-density clusters of the nicotinic acetylcholine receptor (nAChR), with the initiation and maintenance of clustering facilitated by a peripheral membrane protein, rapsyn. Despite the importance of both the nAChR and rapsyn to neuromuscular junction formation and function, structural insight into the rapsyn-nAChR complex and thus how the formation of this complex facilitates clustering is still lacking. In this review, we update our current understanding of nAChR-rapsyn interactions in the context of new structures of the muscle-type nAChR, as well as computationally predicted models of both rapsyn and the nAChR-rapsyn complex. By integrating domain-function studies, biochemical data, and both new and predicted structural data, we present a plausible model of nAChR-rapsyn complex that provides a framework for understanding both clustering at the neuromuscular junction and how mutations in rapsyn lead to the neuromuscular disease, congenital myasthenic syndrome.

PMID:41788248 | PMC:PMC12957682 | DOI:10.1007/s12551-025-01386-8


Source: https://pubmed.ncbi.nlm.nih.gov/4178824 ... t6+133c1fe