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

作者：Gingras Jacinthe; Gawor Marta; Bernadzki Krzysztof M; Grady R Mark; Hallock Peter; Glass David J; Sanes Joshua R; Proszynski Tomasz J^*

来源：Journal of Cell Science, 2016, 129(5): 898-911.

DOI：10.1242/jcs.181180

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

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 alpha-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, alpha-dystrobrevin-1, is required for its function at synapses. We identified a functionally important phosphorylation site on alpha-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 alpha-dystrobrevin-1 in a phosphorylation-independent manner. They include multiple members of the DGC, as well as alpha-catulin, liprin-alpha 1, Usp9x, PI3K, Arhgef5 and Grb2. Finally, we show that two interactors, alpha-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.

• 出版日期2016-3-1