Dystrophin constitutes approximately 5% of the cytoskeletal protein of skeletal muscle sarcolemma, suggesting that dystrophin could play a major structural role in skeletal muscle. We have presented evidence for the existence of a large oligomeric complex containing dystrophin, a 59 kDa triplet, a 25 kDa protein and four sarcolemmal glycoproteins with apparent M(r) of 156 kDa, 50 kDa, 43 kDa and 35 kDa. All components of the dystrophin-glycoprotein complex were localized to the skeletal muscle sarcolemma. Dystrophin, the 156 kDa and 59 kDa dystrophin-associated protein were found to be peripheral membrane proteins while the 50 kDa, 43 kDa, 35 kDa and 25 kDa dystrophin-associated proteins were confirmed as integral membrane proteins. The primary sequences of the 43 kDa and 156 kDa dystrophin-associated glycoproteins have been established by recombinant DNA techniques. Both the 43 and 156 kDa dystrophin-associated glycoproteins are encoded by a single 5.8 kb mRNA which is expressed in a variety of tissues in addition to skeletal muscle. The 156 kDa dystrophin-associated glycoprotein binds laminin, a well characterized component of the extracellular matrix. Finally, the dystrophin-glycoprotein complex is specifically and greatly reduced in Duchenne-afflicted and mdx mouse skeletal muscle, suggesting that the loss of dystrophin-associated proteins is due to the absence of dystrophin and not due to secondary effects of muscle fibre degradation. Taken together, these data support the hypothesis that the absence of dystrophin leads to a loss of the linkage between the subsarcolemmal cytoskeleton and extracellular matrix and that this may initiate muscle fibre necrosis.
|Original language||English (US)|
|Number of pages||28|
|Journal||Molecular and cell biology of human diseases series|
|State||Published - 1993|