ζ-Sarcoglycan is a functional homologue of γ-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. ζ-SG has been recently found as a transmembrane protein homologous to γ-SG and δ-SG. To characterize ζ-SG in complex formation, we co-transfected expression vectors encoding all six SGs (α-, β-, γ-, δ-, ε- and ζ-SG) and dystroglycan into Chinese hamster ovary cells. Immunoprecipitation analysis showed that ζ-SG or γ-SG formed a SGC with β-SG and δ-SG plus α-SG or ε-SG, revealing that ζ-SG can form two types of SGCs (α–β–ζ–δ or ε–β–ζ–δ). This result indicates the functional resemblance of ζ-SG to γ-SG rather than δ-SG, although phylogenetic analysis suggests that ζ-SG is evolutionally closer to δ-SG than to γ-SG. Reverse transcription (RT)-PCR showed that the expression pattern of the transcript was almost the reciprocal of that of γ-SG in various mouse tissues and that the ζ-SG transcript was especially abundant in the brain, suggesting that ζ-SG might play a particular role in the central nervous system.