Dystrobrevin dynamics in muscle-cell signalling: a possible target for therapeutic intervention in Duchenne muscular dystrophy?
The dystrophin-protein complex forms one of the connections between the extracellular matrix and the cytoskeleton of muscle. This link is disrupted in patients with Duchenne and Becker muscular dystrophies. Dystrobrevin is a component of the dystrophin-protein complex that binds to the C-terminus of dystrophin and also to syntrophin. As its name suggests, dystrobrevin is a relative of dystrophin participating in similar intermolecular interactions. Dystrobrevin-deficient mice have a form of muscular dystrophy that leaves the sarcolemma and dystrophin-protein complex intact but affects an as yet unidentified signalling pathway in muscle. Given that the up-regulation of several genes has a beneficial effect on the muscle in some dystrophic mouse models, alpha-dystrobrevin has a number of properties that might be protective in muscular dystrophy. This article discusses the function of dystrobrevin in muscle and reviews its suitability as a therapeutic target for treating patients with Duchenne and Becker muscular dystrophies.
Blake
Derek J
DJ
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK. dblake@enterprise.molbiol.ox.ac.uk
D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism; D016189:Dystrophin / Q000378:metabolism; D049029:Dystrophin-Associated Proteins; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018101:Mice, Inbred mdx; D009124:Muscle Proteins / Q000378:metabolism; D009137:Muscular Dystrophy, Animal / Q000628:therapy; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism* / Q000628:therapy*; D009479:Neuropeptides / Q000378:metabolism*; D015398:Signal Transduction
D003598:Cytoskeletal Proteins; D016189:Dystrophin; D049029:Dystrophin-Associated Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D009479:Neuropeptides; C098885:dystrobrevin; C091824:syntrophin