Towards an understanding of the dystrophin-glycoprotein complex: linkage between the extracellular matrix and the membrane cytoskeleton in muscle fibers.

In muscle, the large membrane cytoskeletal protein dystrophin is tightly associated with several sarcolemmal proteins. It is now well established that the extracellular 156 kDa dystrophin-associated glycoprotein alpha-dystroglycan is a laminin binding protein which is linked to the sarcolemma via an integral glycoprotein complex. Beta-dystroglycan of 43 kDa, together with the 50 kDa protein adhalin and three other dystrophin-associated glycoproteins of 25, 35 and 43 kDa form this sarcolemmal complex which binds to the cysteine-rich domain of dystrophin. While the carboxy-terminal domain of dystrophin is associated with the syntrophin triplet of apparent 59 kDa, the amino-terminal dystrophin domain binds to the subsarcolemmal actin cytoskeleton. Numerous studies into the molecular pathogenesis of muscular dystrophies and cardiomyopathies suggest that primary defects in components of the dystrophin-glycoprotein complex are responsible for certain forms of these muscular disorders. Disturbances in the composition of the dystrophin-glycoprotein complex in skeletal and cardiac muscle seem to disrupt the linkage between the extracellular matrix and the actin membrane cytoskeleton which might render muscle fibers more susceptible to necrosis. In normal muscle, the vital function of the dystrophin-glycoprotein complex appears to be the stabilization of the muscle cell periphery during contraction.