α-Dystrobrevin-1 recruits Grb2 and α-catulin to organize neurotransmitter receptors at the neuromuscular junction

Jacinthe Gingras, Marta Gawor, Krzysztof M. Bernadzki, R. Mark Grady, Peter Hallock, David J. Glass, Joshua R. Sanes, Tomasz J. Proszynski

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Neuromuscular junctions (NMJs), the synapses made by motor neurons on muscle fibers, form during embryonic development but undergo substantial remodeling postnatally. Several lines of evidence suggest that a-dystrobrevin, a component of the dystrophinassociated glycoprotein complex (DGC), is a crucial regulator of the remodeling process and that tyrosine phosphorylation of one isoform, α-dystrobrevin-1, is required for its function at synapses. We identified a functionally important phosphorylation site on α-dystrobrevin-1, generated phosphorylation-specific antibodies to it and used them to demonstrate dramatic increases in phosphorylation during the remodeling period, as well as in nerve-dependent regulation in adults. We then identified proteins that bind to this site in a phosphorylation-dependent manner and others that bind to α-dystrobrevin-1 in a phosphorylation-independent manner. They include multiple members of the DGC, as well as α-catulin, liprin-a1, Usp9x, PI3K, Arhgef5 and Grb2. Finally, we show that two interactors, α-catulin (phosphorylation independent) and Grb2 (phosphorylation dependent) are localized to NMJs in vivo, and that they are required for proper organization of neurotransmitter receptors on myotubes.

Original languageEnglish
Pages (from-to)898-911
Number of pages14
JournalJournal of cell science
Volume129
Issue number5
DOIs
StatePublished - 2016

Keywords

  • AChR
  • Development
  • Dystrobrevin
  • Dystrophin-associated glycoprotein complex
  • Maturation
  • Neuromuscular junction

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