Signals mediating ion channel clustering at the neuromuscular junction

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Abstract

High densities of acetylcholine receptors and sodium channels in the crest and troughs of the postsynaptic folds, respectively ensure reliable neuromuscular signalling. Clustering of both ion channels is mediated by agrin. In the case of acetylcholine receptors, agrin activates the tyrosine kinase receptor muscle-specific kinase (MuSK), initiating a process requiring rapsyn and possibly also receptor phosphorylation. In many respects, the interactions between agrin and MuSK and their downstream effectors are atypical of conventional receptor tyrosine kinase signalling systems. A new understanding of the structural features of rapsyn involved in receptor clustering, as well as syntrophin's role in sodium channel targeting, has recently been revealed. Perhaps the most surprising result of the past year with regard to synaptogenesis is a negative one — mice lacking both dystrophin and utrophin have nearly normal neuromuscular junctions.

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