Sarcoglycans in muscular dystrophy

Muscular dystrophy is a heterogeneous genetic disease that affects skeletal and cardiac muscle. The genetic defects associated with muscular dystrophy include mutations in dystrophin and its associated glycoproteins, the sarc oglycans. Furthermore, defects in dystrophin have been shown to cause a dis ruption of the normal expression and localization of the sarcoglycan comple x. Thus, abnormalities of sarcoglycan are a common molecular feature in a n umber of dystrophies. By combining biochemistry, molecular cell biology, an d human and mouse genetics, a growing understanding of the sarcoglycan comp lex is emerging. Sarcoglycan appears to be an important, independent mediat or of dystrophic pathology in both skeletal muscle and heart. The absence o f sarcoglycan leads to alterations of membrane permeability and apoptosis, two shared features of a number of dystrophies. beta-sarcoglycan and delta- sarcoglycan may form the core of the sarcoglycan subcomplex with alpha- and gamma-sarcoglycan less tightly associated to this core. The relationship o f epsilon-sarcoglycan to the dystrophin-glycoprotein complex remains unclea r. Animals lacking alpha-, gamma- and delta-sarcoglycan have been described and provide excellent opportunities for further investigation of the funct ion of sarcoglycan. Dystrophin with dystroglycan and laminin may be a mecha nical link between the actin cytoskeleton and the extracellular matrix. By positioning itself in close proximity to dystrophin and dystroglycan, sarco glycan may function to couple mechanical and chemical signals in striated m uscle. Sarcoglycan may be an independent signaling or regulatory module who se position in the membrane is determined by dystrophin but whose function is carried out independent of the dystrophin-dystroglycan-laminin axis. (C) 2000 Wiley-Liss, Inc.