The β-δ-core of sarcoglycan is essential for deposition at the plasma membrane

Abstract

Mutations of any of the sarcoglycan complex subunits (α, β, δ, and γ) cause limb-girdle muscular dystrophy. Furthermore, individual mutations lead to a reduction or loss of all other members of the complex. In some cases of limb-girdle muscular dystrophies, however, residual sarcoglycan expression has been documented. Therefore, in this study we tested the hypothesis that formation of specific sarcoglycan subcomplexes is crucial for plasma membrane deposition. Using co-immunoprecipitation assays, we demonstrated that β- and δ-sarcoglycan interact with α-sarcoglycan and these two subunits must be co-expressed for export from the endoplasmic reticulum. Advanced light-microscopic imaging techniques demonstrated that co-expression of β-sarcoglycan and δ-sarcoglycan is also responsible for delivery to and retention of sarcoglycan subcomplexes at the cell surface. These data suggest that formation of the β-δ-core may promote the export and deposition of sarcoglycan subcomplexes at the plasma membrane, and therefore identifies a mechanism for sarcoglycan transport. © 2006 Wiley Periodicals, Inc.