L-type calcium channels mediate acetylcholine receptor aggregation on cultured muscle

Rebecca B.R. Milholland, Christopher Dulla, Herman Gordon

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Agrin activation of muscle specific kinase (MuSK) initiates postsynaptic development on skeletal muscle that includes the aggregation of acetylcholine receptors (AChRs; Glass et al. [1996]: Cell 85: 513-523; Gautam et al. [1996]: Cell 85: 525-535). Although the agrin/MuSK signaling pathway remains largely unknown, changes in intracellular calcium levels are required for agrin-induced AChR aggregation (Megeath and Fallon [1998]: J Neurosci 18: 672-678). Here, we show that L-type calcium channels (L-CaChs) are required for full agrin-induced aggregation of AChRs and sufficient to induce agrin-independent AChR aggregation. Blockade of L-CaChs in muscle cultures inhibited agrin-induced AChR aggregation but not tyrosine phosphorylation of MuSK or AChR β subunits. Activation of L-CaChs in the absence of agrin induced AChR aggregation but not tyrosine phosphorylation of MuSK or AChR β subunits. Agrin responsiveness was significantly reduced in primary muscle cultures from the muscular dysgenesis mouse, a natural mutant, which does not express the L-CaCh. Our results establish a novel role for L-CaChs as important sources of the intracellular calcium necessary for the aggregation of AChRs.

Original languageEnglish (US)
Pages (from-to)987-998
Number of pages12
JournalDevelopmental Neurobiology
Volume67
Issue number8
DOIs
StatePublished - Jul 1 2007

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Keywords

  • Acetylcholine receptor
  • Aggregation
  • Agrin
  • Calcium
  • Cluster
  • Dysgenic mouse
  • Intracellular signaling
  • L-type calcium channel
  • MuSK
  • Muscle specific kinase
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

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