[zeta]-Sarcoglycan is a functional homologue of gamma -sarcoglycan in the formation of the sarcoglycan complex

The sarcoglycans (SGs), transmembrane components of the dystrophin-associated glycoprotein complex, are stable and functional only when they assemble into a tetrameric complex in muscle cells. A defect in any one of the four SG members disrupts the entire SG complex (SGC) and causes limb-girdle muscular dystrophy. [zeta]-SG has been recently found as a transmembrane protein homologous to gamma -SG and delta -SG. To characterize [zeta]-SG in complex formation, we co-transfected expression vectors encoding all six SGs ( alpha -, beta -, gamma -, delta -, epsilon - and [zeta]-SG) and dystroglycan into Chinese hamster ovary cells. Immunoprecipitation analysis showed that [zeta]-SG or gamma -SG formed a SGC with beta -SG and delta -SG plus alpha -SG or epsilon -SG, revealing that [zeta]-SG can form two types of SGCs ( alpha - beta -[zeta]- delta or epsilon - beta -[zeta]- delta ). This result indicates the functional resemblance of [zeta]-SG to gamma -SG rather than delta -SG, although phylogenetic analysis suggests that [zeta]-SG is evolutionally closer to delta -SG than to gamma -SG. Reverse transcription (RT)-PCR showed that the expression pattern of the transcript was almost the reciprocal of that of gamma -SG in various mouse tissues and that the [zeta]-SG transcript was especially abundant in the brain, suggesting that [zeta]-SG might play a particular role in the central nervous system.