Agrin-induced phosphorylation of the acetylcholine receptor regulates cytoskeletal anchoring and clustering

Lúcia S. Borges, Michael J Ferns

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

At the developing neuromuscular junction, a motoneuron-derived factor called agrin signals through the muscle-specific kinase receptor to induce post-synaptic aggregation of the acetylcholine receptor (AChR). The agrin signaling pathway involves tyrosine phosphorylation of the AChR β subunit, and we have tested its role in receptor localization by expressing tagged, tyrosine-minus forms of the β subunit in mouse Sol8 myotubes. We find that agrin-induced phosphorylation of the β subunit occurs only on cell surface AChR, and that AChR-containing tyrosine-minus β subunit is targeted normally to the plasma membrane. Surface AChR that is tyrosine phosphorylated is less detergent extractable than nonphosphorylated AChR, indicating that it is preferentially linked to the cytoskeleton. Consistent with this, we find that agrin treatment reduces the detergent extractability of AChR that contains tagged wild-type β subunit but not tyrosine-minus β subunit. In addition, agrin-induced clustering of AChR containing tyrosine-minus β subunit is reduced in comparison to wild-type receptor. Thus, we find that agrin-induced phosphorylation of AChR β subunit regulates cytoskeletal anchoring and contributes to the clustering of the AChR, and this is likely to play an important role in the postsynaptic localization of the receptor at the developing synapse.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalJournal of Cell Biology
Volume153
Issue number1
DOIs
StatePublished - Apr 2 2001
Externally publishedYes

Keywords

  • Agrin
  • Cytoskeleton
  • Neuromuscular junction
  • Synaptogenesis
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Cell Biology

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