Dystrophin‐Associated Proteins and the Muscular Dystrophies: A Glossary

The Dystrophin-Associated Protein ComplexRecent advances in understanding the muscular dystrophies illustrate the powerful reciprocal interaction between investigations of molecular pathogenesis of diseases (e.g.Duchenne muscular dystrophy or DMD) and basic problems in molecular biology (e.g. the molecular composition of the muscle membrane).In less than a decade, studies of DMD have led to the discovery not only of dystrophin ( 17) but also of an expanding family of dystrophin-associated proteins (9,38), as summarized in Figure 1.Increasingly, defects in the genes encoding these proteins have been identified as the cause of diverse forms of muscular dystrophy.As recently reviewed (26,31,36), it is instructive to consider the dystrophin-associated proteins in three major groups: the dystroglycan complex proteins, the sarcoglycan proteins and the syntrophins.77ie extraceZliilar nintrix and dystroglycnn cowlplex.At its extracellular face, skeletal muscle is enmeshed in the extracellular matrix (ECM), a complex network composed of collagen, laminin and proteoglycans.Skeletal muscle laminin is a heterotrimer, composed of pl-, yl-u2-laminin subunits.u2-laminin is also designated merosin.The laminin complex binds to sugar moieties of the glycoprotein dystroglycan at the muscle cell surface (10).Two subunits generated by proteolytic cleavage from a single precursor protein comprise dystroglycan: a-dystroglycan (156 kd) and P-dystroglycan (43 kd) (39).adystroglycan is believed to be extracellular while Pdystroglycan spans the muscle membrane.These two subunits bind one another.Moreover, at the cytoplasmic face of the membrane, p-dystroglycan