Agrin-independent activation of the agrin signal transduction pathway

Wade A. Grow, Michael Ferns, Herman Gordon

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

The neural factor agrin induces the aggregation of acetylcholine receptors (AChRs) and other synaptic molecules on cultured myotubes. This aggregating activity can be mimicked by experimental manipulations that include treatment with neuraminidase or elevated calcium. We report evidence that neuraminidase and calcium act through the agrin signal transduction pathway. The effects of neuraminidase and calcium on AChR clustering are additive with that of agrin at low concentrations and cosaturating at high concentrations. In addition, like agrin, both neuraminidase and calcium cause rapid tyrosine phosphorylation of the muscle-specific kinase (MUSK) and the AChR-β subunit. Our results argue that all three agents act directly on components of the same signal transduction complex. We suggest that sialic acids on components of the complex inhibit interactions necessary for signal transduction and that disinhibition can result in activation. In such a model, agrin could activate signal transduction by disinhibition or by circumventing the inhibition.

Original languageEnglish (US)
Pages (from-to)356-365
Number of pages10
JournalJournal of Neurobiology
Volume40
Issue number3
DOIs
StatePublished - Aug 23 1999

Keywords

  • Acetylcholine receptor
  • Agrin
  • C2C12
  • Calcium
  • MUSK
  • Neuraminidase
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience

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