Dual role for calcium in agrin signaling and acetylcholine receptor clustering

L. S. Borges, Y. Lee, Michael J Ferns

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Agrin is a motoneuron-derived factor that initiates neuromuscular synapse formation; however, the signaling pathway underlying postsynaptic differentiation is not yet understood. We have investigated the role of calcium in agrin signaling through the MuSK receptor tyrosine kinase and in the intracellular signaling cascade that leads to AChR phosphorylation and clustering. We find that agrin- and neuramindase-induced MuSK activation in cultured myotubes is completely blocked by removal of extracellular calcium, but only slightly reduced by clamping of intracellular calcium transients with BAPTA. Following agrin's activation of MUSK, we find that the downstream tyrosine phosphorylation of the AChR β-subunit was inhibited by BAPTA but not by a slower acting chelator, EGTA. Similarly, agrin-induced clustering of the AChR was blocked by BAPTA but not EGTA. These findings indicate that extracellular calcium is required for the formation of a MuSK signaling complex, and that intracellular calcium regulates phosphorylation and clustering of the AChR in the postsynaptic membrane.

Original languageEnglish (US)
Pages (from-to)69-79
Number of pages11
JournalJournal of Neurobiology
Volume50
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Acetylcholine receptor clustering
  • Agrin signaling
  • Calcium

ASJC Scopus subject areas

  • Neuroscience(all)

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