Agrin-induced acetylcholine receptor clustering in mammalian muscle requires tyrosine phosphorylation

Michael J Ferns, Michael Deiner, Zach Hall

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Abstract

Agrin is thought to be the nerve-derived factor that initiates acetylcholine receptor (AChR) clustering at the developing neuromuscular junction. We have investigated the signaling pathway in mouse C2 myotubes and report that agrin induces a rapid but transient tyrosine phosphorylation of the AChR β subunit. As the β-subunit tyrosine phosphorylation occurs before the formation of AChR clusters, it may serve as a precursor step in the clustering mechanism. Consistent with this, we observed that tyrosine phosphorylation of the β subunit correlated precisely with the presence or absence of clustering under several experimental conditions. Moreover, two tyrosine kinase inhibitors, herbimycin and staurosporine, that blocked β- subunit phosphorylation also blocked agrin-induced clustering. Surprisingly, the inhibitors also dispersed preformed AChR clusters, suggesting that the tyrosine phosphorylation of other proteins may be required for the maintenance of receptor clusters. These findings indicate that in mammalian muscle, agrin-induced AChR clustering occurs through a mechanism that requires tyrosine phosphorylation and may involve tyrosine phosphorylation of the AChR itself.

Original languageEnglish (US)
Pages (from-to)937-944
Number of pages8
JournalJournal of Cell Biology
Volume132
Issue number5
DOIs
StatePublished - Mar 1996

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ASJC Scopus subject areas

  • Cell Biology

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