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

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.

Pubmed ID: 10559919


  • Grady RM
  • Grange RW
  • Lau KS
  • Maimone MM
  • Nichol MC
  • Stull JT
  • Sanes JR


Nature cell biology

Publication Data

August 8, 1999

Associated Grants


Mesh Terms

  • Animals
  • Dystrophin
  • Dystrophin-Associated Proteins
  • Genotype
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred mdx
  • Mice, Knockout
  • Models, Biological
  • Muscle, Skeletal
  • Muscular Dystrophy, Animal
  • Mutation
  • Neuropeptides
  • Phenotype
  • Signal Transduction