Role for α-dystrobrevin in the pathogenesis of dystrophin-dependent muscular dystrophies
Author: ["R. Mark Grady","Robert W. Grange","Kim S. Lau","Margaret M. Maimone","Mia C. Nichol","James T. Stull","Joshua R. Sanes"]
Publication: Nature Cell Biology
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Abstract
A dystrophin-containing glycoprotein complex (DGC) links the basal lamina surrounding each muscle fibre to the fibre’s cytoskeleton, providing both structural support and a scaffold for signalling molecules. Mutations in genes encoding several DGC components disrupt the complex and lead to muscular dystrophy. Here we show that mice deficient in α-dystrobrevin, a cytoplasmic protein of the DGC, exhibit skeletal and cardiac myopathies. Analysis of double and triple mutants indicates that α-dystrobrevin acts largely through the DGC. Structural components of the DGC are retained in the absence of α-dystrobrevin, but a DGC-associated signalling protein, nitric oxide synthase, is displaced from the membrane and nitric-oxide-mediated signalling is impaired. These results indicate that both signalling and structural functions of the DGC are required for muscle stability, and implicate α-dystrobrevin in the former.
Cite this article
Grady, R., Grange, R., Lau, K. et al. Role for α-dystrobrevin in the pathogenesis of dystrophin-dependent muscular dystrophies. Nat Cell Biol 1, 215–220 (1999). https://doi.org/10.1038/12034
