A sarcoglycan-dystroglycan complex anchors Dp116 and utrophin in the peripheral nervous system

The dystrophin-associated membrane-integrated protein complex anchors dystr ophin in the sarcolemma of striated muscles and is composed of two glycopro tein subcomplexes, the dystroglycan and the sarcoglycan (SG) complexes, and a small membrane protein termed sarcospan (SPN). The SG complex consists o f four transmembrane glycoproteins, alpha -SG, beta -SG, gamma -SG and delt a -SG. We found that beta -SG and delta -SG were co-expressed with epsilon -SG, a alpha -SG homolog, in the peripheral nerve, but not with alpha -SG o r gamma -SG. SPN, which tightly links to the SG complex in the muscle cell membrane, was absent in the peripheral nerve, These peripheral nerve SGs we re colocalized at the outermost layer of the myelin sheath of nerve fibers together with the dystroglycan complex, utrophin, and a short dystrophin is oform (Dp116). Immunocytochemical analysis using SG-deficient animals showe d that a defect in beta- or delta -SG led to a great reduction of all resid ual SGs, but not of the other proteins, i.e., dystroglycans, Dp116 and utro phin, in the peripheral nerve. This observation suggests that the epsilon-, beta- and delta -SG molecules form a complex behaving as a single unit sim ilar to the SG complex in muscle cells. An immunoprecipitation study indica ted that the SG complex is associated with the dystroglycan complex and Dp1 16 or utrophin, These results demonstrated that Dp116 and utrophin are anch ored to a novel membrane protein architecture, which consists of the SG and dystroglycan complexes, but not SPN, in the Schwann cell membrane.