Sarcoglycan isoforms in skeletal muscle

The heterotetrameric sarcoglycan complex, composed of alpha-, beta-, gamma- , and delta-sarcoglycans, is an important component of the dystrophin-assoc iated glycoprotein assembly in striated muscle, Mutations in any of the fou r genes encoding sarcoglycans cause a deficiency in all sarcoglycans in the sarcolemma and produce one of four types of limb-girdle muscular dystrophy . A fifth widely expressed sarcoglycan, epsilon-sarcoglycan, has been recen tly described. epsilon-Sarcoglycan is homologous to alpha-sarcoglycan, but whether it associates with the other sarcoglycans in muscle is not known. I n this study, we use wild type and alpha-sarcoglycan-deficient mice to anal yze the localization and association of sarcoglycans in skeletal muscle in vivo. The amounts of beta-, gamma-, and delta-sarcoglycans are reduced in a lpha-sarcoglycan mutants, whereas the amount of epsilon-sarcoglycan is unch anged, We show here that epsilon-sarcoglycan is complexed with beta-, gamma -, and delta-sarcoglycans in both wild type and alpha-sarcoglycan mutant mi ce, We also use C2C12 myocytes to study the temporal expression and organiz ation of sarcoglycan complexes during muscle cell differentiation in vitro. In C2C12 cells, alpha- and epsilon-sarcoglycans form separate complexes wi th beta-, gamma-, and delta-sarcoglycans, Both types of complexes are expre ssed at the cell surface and presumed to be functional, These results sugge st that epsilon-sarcoglycan serves a function similar to that of alpha-sarc oglycan and that residual beta-, gamma-, and delta-sarcoglycan seen in muta nt mice and epsilon-sarcoglycan-deficient patients is due to its associatio n with epsilon-sarcoglycan.