Role for α-dystrobrevin in the pathogenesis of dystrophin-dependent muscular dystrophies
| Autor: | Joshua R. Sanes, R. Mark Grady, James T. Stull, Mia C. Nichol, Robert W. Grange, Kim S. Lau, Margaret M. Maimone |
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| Rok vydání: | 1999 |
| Předmět: |
Genotype
Biology Models Biological Dystrophin Dystrophin-associated glycoprotein complex Mice Dystrophin-associated protein complex Glycoprotein complex Dystrobrevin medicine Animals Muscular dystrophy Muscle Skeletal Syntrophin Mice Knockout Neuropeptides Cell Biology Muscular Dystrophy Animal medicine.disease Dystrophin-associated protein Cell biology Mice Inbred C57BL Phenotype Dystrophin-Associated Proteins Mutation Mice Inbred mdx biology.protein Signal Transduction |
| Zdroj: | Nature Cell Biology. 1:215-220 |
| ISSN: | 1476-4679 1465-7392 |
| DOI: | 10.1038/12034 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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