alpha-Dystrobrevin is both a dystrophin homologue and a component of the dystrophin protein complex. Alternative splicing yields five forms, of which two predominate in skeletal muscle: full-length alpha-dystrobrevin-1 (84 kD), and COOH-terminal truncated alpha-dystrobrevin-2 (65 kD). Using isoform-specific antibodies, we find that alpha-dystrobrevin-2 is localized on the sarcolemma and at the ...

a -Dystrobrevin is both a dystrophin homologue and a component of the dystrophin protein complex. Alternative splicing yields five forms, of which two predominate in skeletal muscle: full-length a -dystrobrevin-1 (84 kD), and COOH-terminal truncated a -dystrobrevin-2 (65 kD). Using isoform-specific antibodies, we find that a -dystrobrevin-2 is localized on the sarcolemma and at the neuromuscula...

Mutations in the human dystrophin gene cause the Duchenne and Becker muscular dystrophies. The Dystrophin protein provides a structural link between the muscle cytoskeleton and extracellular matrix to maintain muscle integrity. Recently, Dystrophin has also been found to act as a scaffold for several signaling molecules, but the roles of dystrophin-mediated signaling pathways remain unknown. To...

Dystrophin is responsible for the mechanical stabilization of the sarcolemma, and it has been shown that it is one of the most sensitive proteins to ischemic injury. However, the enzyme responsible for this proteolysis is still unknown. Isolated rabbit hearts were subjected to 30 min of global ischemia with and without reperfusion (180 min) to determine whether dystrophin is cleaved by matrix m...

We studied the location, relative abundance, and stability of dystrophin in clusters of ACh receptors (AChRs) isolated from primary cultures of neonatal rat myotubes. Although variable amounts of dystrophin were found at receptor clusters, dystrophin was always associated with organized, receptor-rich domains (AChR domains). Dystrophin was occasionally seen in focal contact domains, but never i...

Duchenne muscular dystrophy (DMD) is a severe progressive muscular disorder caused by reading frame disrupting mutations in the DMD gene, preventing the synthesis of functional dystrophin. As dystrophin provides muscle fiber stability during contractions, dystrophin negative fibers are prone to exercise-induced damage. Upon exhaustion of the regenerative capacity, fibers will be replaced by fib...

Becker muscular dystrophy is an X-linked disease due to mutations of the dystrophin gene. We now show that neuronal-type nitric oxide synthase (nNOS), an identified enzyme in the dystrophin complex, is uniquely absent from skeletal muscle plasma membrane in many human Becker patients and in mouse models of dystrophinopathy. An NH2-terminal domain of nNOS directly interacts with alpha 1-syntroph...

Duchenne muscular dystrophy (DMD) is a fatal disease caused by defects in the gene encoding dystrophin. Dystrophin is a cytoskeletal protein, which together with its associated protein complex, helps to protect the sarcolemma from mechanical stresses associated with muscle contraction. Gene therapy efforts aimed at supplying a normal dystrophin gene to DMD muscles could be hampered by host immu...

Duchenne muscular dystrophy (DMD) is a fatal muscle wasting disorder caused by mutations in the dystrophin gene. DMD has a complex and as yet incompletely defined molecular pathophysiology. The peak of the pathology attributed to dystrophin deficiency happens between 3 and 8 weeks of age in mdx mice, the animal model of DMD. Accordingly, we hypothesized that the pathology observed with dystroph...

Mutations in the dystrophin gene result in Duchenne muscular dystrophy (DMD). Dystrophin is a multidomain protein that functions to stabilize the sarcolemmal membrane during muscle contraction. The central rod domain has been proposed to act as a shock absorber, as a force transducer or as a spacer separating important Nand C-terminal domains that interact with actin and the dystrophin–glycopro...