Sarcoglycan isoforms in skeletal muscle

Abstract

The heterotetrameric sarcoglycan complex, composed of α-, β-, γ-, and δ-sarcoglycans, is an important component of the dystrophin-associated glycoprotein assembly in striated muscle. Mutations in any of the four 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, ε-sarcoglycan, has been recently described. ε-Sarcoglycan is homologous to α-sarcoglycan, but whether it associates with the other sarcoglycans in muscle is not known. In this study, we use wild type and α-sarcoglycan-deficient mice to analyze the localization and association of sarcoglycans in skeletal muscle in vivo. The amounts of β-, γ-, and δ-sarcoglycans are reduced in α-sarcoglycan mutants, whereas the amount of ε-sarcoglycan is unchanged. We show here that ε-sarcoglycan is complexed with β-, γ-, and δ-sarcoglycans in both wild type and α-sarcoglycan mutant mice. We also use C2C12 myocytes to study the temporal expression and organization of sarcoglycan complexes during muscle cell differentiation in vitro. In C2C12 cells, α- and ε-sarcoglycans form separate complexes with β-, γ-, and δ-sarcoglycans. Both types of complexes are expressed at the cell surface and presumed to be functional. These results suggest that ε-sarcoglycan serves a function similar to that of α-sarcoglycan and that residual β-, γ-, and δ-sarcoglycan seen in mutant mice and α-sarcoglycan-deficient patients is due to its association with ε-sarcoglycan.