Expression of gamma-sarcoglycan in smooth muscle and its interaction with the smooth muscle sarcoglycan-sarcospan complex

The sarcoglycan complex in striated muscle is a heterotetrameric unit integ rally associated with sarcospan in the dystrophin-glycoprotein complex. The sarcoglycans, alpha, beta, gamma, and delta, are mutually dependent with r egard to their localization at the sarcolemma, and mutations in any of the sarcoglycan genes lead to limb-girdle muscular dystrophies type 2C-2F. In s mooth muscle beta- and delta -sarcoglycans are associated with epsilon -sar coglycan, a glycoprotein homologous to alpha -sarcoglycan. Here, we demonst rate that gamma -sarcoglycan is also a component of the sarcoglycan complex in the smooth muscle. First, we show the presence of gamma -sarcoglycan in a number of smooth muscle containing organs, and we verify the existence o f identical transcripts in skeletal and smooth muscle. The specificity of t he expression of gamma -sarcoglycan in smooth muscle was confirmed by analy sis of smooth muscle cells in culture. Next, we provide evidence for the as sociation of gamma -sarcoglycan with the sarcoglycan-sarcospan complex by b iochemical analysis and comparison among animal models for muscular dystrop hy. Moreover, we find disruption of the sarcoglycan complex in the vascular smooth muscle of a patient with gamma -sarcoglycanopathy. Taken together, our results prove that the sarcoglycan complex in vascular and visceral smo oth muscle consists of epsilon- beta-, gamma-, and delta -sarcogIycans and is associated with sarcospan.