• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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

Authors

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

Journal

Nature cell biology

Publication Data

August 8, 1999

Associated Grants

None

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