Following the discovery of the primary genetic abnormality in Duchenne muscular dystrophy, i.e. mutations in the gene encoding the Dp427 isoform of the protein dystrophin, biochemical analyses showed that this membrane cytoskeletal element exists in a large heterogeneous membrane complex. Due to the fact that glycoproteins associated with this complex are involved in the pathophysiology of numerous neuromuscular disorders, an extensive characterization of the dystrophin-associated glycoprotein complex was initiated in the last decade. This review summarizes the structure and function of the dystrophin-glycoprotein complex with special emphasis on the role of dystroglycans, sarcoglycans, sarcospan, dystrobrevins, and syntrophins in normal and diseased skeletal muscle fibres. Besides being involved in the stabilization of the muscle periphery by linking the extracellular matrix to the membrane cytoskeleton, the dystrophin complex appears also to be involved in signal transduction mechanisms. The functional connection between the dystrophin-glycoprotein complex and enzymes such as the neuronal nitric oxide synthase and different classes of ion channels is discussed.
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