Acetylcholine receptors are required for postsynaptic aggregation driven by the agrin signalling pathway

Wade A. Grow, Herman Gordon

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

To investigate the role of acetylcholine receptors (AChRs) in the aggregation of postsynaptic molecules on muscle cells, we utilized the 1R- genetic variant of C2 muscle cells which has very little expression of AChRs in its cell membrane. On C2 myotubes, AChRs cluster spontaneously, with the frequency of clustering greatly enhanced by motor neuron-derived agrin. Signal transduction events driven by agrin, including the tyrosine phosphorylation of muscle-specific kinase (MuSK) and the AChR β subunit, have been implicated as requirements of postsynaptic scaffold assembly. We show here that some molecules of the postsynaptic scaffold spontaneously aggregate and colocalize on 1R- myotubes at very low frequency, including an as yet unidentified agrin binding molecule, β-dystroglycan and MuSK. Agrin is unable to increase the frequency of these aggregations, but does cause tyrosine phosphorylation of MuSK. We conclude that free molecules can associate into aggregates independently of AChRs, but AChRs are required for high-frequency molecular aggregation driven by the agrin signalling pathway. MuSK tyrosine phosphorylation appears to precede a requisite event involving AChRs that aggregates postsynaptic molecules.

Original languageEnglish (US)
Pages (from-to)467-472
Number of pages6
JournalEuropean Journal of Neuroscience
Volume12
Issue number2
DOIs
StatePublished - Mar 22 2000

Keywords

  • 1R myotubes
  • C2 myotubes
  • MuSK
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Neuroscience(all)

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