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

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 ?-dystrobrevin, a component of the dystrophin-associated glycoprotein complex (DGC), is a crucial regulator of the remodeling process and that tyrosine phosphorylation of one isoform, ?-dystrobrevin-1, is required for its function at synapses. We identified a functionally important phosphorylation site on ?-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 ?-dystrobrevin-1 in a phosphorylation-independent manner. They include multiple members of the DGC, as well as ?-catulin, liprin-?1, Usp9x, PI3K, Arhgef5 and Grb2. Finally, we show that two interactors, ?-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.

SUBMITTER: Gingras J 

PROVIDER: S-EPMC4813319 | biostudies-other | 2016 Mar

REPOSITORIES: biostudies-other