Another type of cell-ECM connection is the dystrophin glycoprotein complex (DGC) of skeletal muscle cells. Similar complexes are found in smooth muscle and in some non-muscle tissues. Muscle cells, of course are subject to frequent mechanical stress, and connectivity to the ECM is important in supporting the cell integrity. The DGC uses the large transmembrane glycoprotein, dystroglycan, as its primary binding partner to basal lamina laminin. A sarcoglycan complex and sarcospan are other major transmembrane components of the DGC, but their roles do not appear to include direct interaction with basal lamina.
The sarcoglycan complex (consisting of 4 sarcoglycans) is postulated to act as structural reinforcement for the membrane at these contact points. The role of sarcospan, a 4-pass transmembrane protein, has not been demonstrated within the DGC, but homologous proteins in other cells are found in adhesive complexes with integrin receptors, suggesting the same function here. Although the DGCs are long-lived adhesive contact that have more in common with hemidesmosomes than focal contacts, the cytoskeletal component attached to the DGC is actin (via dystrophin), not intermediate laments. However, it is important to note that the actin cytoskeleton of muscle cells has very different functions from its counterpart in a fibroblast. Mutations to the sarcoglycans, dystroglycan, and dystrophin have all been shown to cause muscular dystrophies.
Mutations leading to loss of sarcospan have not been linked to any muscular dystrophies. However, sarcospan is not found in muscular dystrophy patients who have mutations in the sarcoglycans. It thus appears that the tetrameric sarcoglycan complex is required for normal membrane localization of sarcospan.