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Nat Cell Biol. 1999 Aug;1(4):215-20.

Role for alpha-dystrobrevin in the pathogenesis of dystrophin-dependent muscular dystrophies.

Author information

1
Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110, USA. grady@a1.kids.wustl.edu

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 alpha-dystrobrevin, a cytoplasmic protein of the DGC, exhibit skeletal and cardiac myopathies. Analysis of double and triple mutants indicates that alpha-dystrobrevin acts largely through the DGC. Structural components of the DGC are retained in the absence of alpha-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 alpha-dystrobrevin in the former.

PMID:
10559919
DOI:
10.1038/12034
[Indexed for MEDLINE]

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