Article abstract
Nature Cell Biology 1, 215 - 220 (1999)
Published online: 8 July 1999 | doi:10.1038/12034
Role for 
-dystrobrevin in the pathogenesis of dystrophin-dependent
muscular dystrophies
R. Mark Grady1, Robert W. Grange2, Kim S. Lau2, Margaret M. Maimone3,4, Mia C. Nichol5, James T. Stull2 & Joshua R. Sanes5
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 
-dystrobrevin,
a cytoplasmic protein of the DGC, exhibit skeletal and cardiac myopathies.
Analysis of double and triple mutants indicates that -dystrobrevin
acts largely through the DGC. Structural components of the DGC are retained
in the absence of -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 -dystrobrevin in the former.
- Department of Pediatrics, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA
- Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas , Texas 75235, USA
- Department of Molecular Biology and Pharmacology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA
- Department of Anatomy and Cell Biology, SUNY Syracuse , Syracuse, New York 13210, USA
- Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 S. Euclid Avenue, St Louis, Missouri 63110, USA
Correspondence to: R. Mark Grady1 e-mail: grady@a1.kids.wustl.edu
