ε-Sarcoglycan replaces α-sarcoglycan in smooth muscle to form a unique dystrophin-glycoprotein complex

Abstract

The sarcoglycan complex has been well characterized in striated muscle, and defects in its components are associated with muscular dystrophy and cardiomyopathy. Here, we have characterized the smooth muscle sarcoglycan complex. By examination of embryonic muscle lineages and biochemical fractionation studies, we demonstrated that ε-sarcoglycan is an integral component of the smooth muscle sarcoglycan complex along with β- and δ- sarcoglycan. Analysis of genetically defined animal models for muscular dystrophy supported this conclusion. The δ-sarcoglycan-deficient cardiomyopathic hamster and mice deficient in both dystrophin and utrophin showed loss of the smooth muscle sarcoglycan complex, whereas the complex was unaffected in α-sarcoglycan null mice in agreement with the finding that α- sarcoglycan is not expressed in smooth muscle cells. In the cardiomyopathic hamster, the smooth muscle sarcoglycan complex, containing ε-sarcoglycan, was fully restored following intramuscular injection of recombinant δ- sarcoglycan adenovirus. Together, these results demonstrate a tissue- dependent variation in the sarcoglycan complex and show that ε-sarcoglycan replaces α-sarcoglycan as an integral component of the smooth muscle dystrophin-glycoprotein complex. Our results also suggest a molecular basis for possible differential smooth muscle dysfunction in sarcoglycan-deficient patients.