The sarcoglycan complex in skeletal muscle.

Frontiers in bioscience (Landmark edition) 2016 Jan 01

In skeletal muscle, the dystrophin-associated glycoprotein complex forms a link between the actin cytoskeleton and the extracellular matrix that is critical for muscle integrity. Within this complex resides the sarcoglycan subcomplex, which consists of four transmembrane glycoproteins (alpha-, beta-, gamma-, and delta-sarcoglycan). During assembly, beta-sarcoglycan tightly associates with delta-sarcoglycan to form a functional core that then recruits gamma- and alpha-sarcoglycan to form the sarcoglycan complex. Together with sarcospan, the sarcoglycan complex binds other components of the dystrophin-associated glycoprotein complex and integrates into the myofibre's membrane. Once integrated, the sarcoglycan complex plays a pivotal role in mechanically stabilising the sarcolemma as well as the dystrophin-associated glycoprotein complex. Additionally, the sarcoglycan complex undergoes chemical modifications in response to muscle contractions, thereby transducing mechanical information into a cellular signal. Mutations in the sarcoglycans induce limb girdle muscular dystrophy, and several animal models have been established to study the molecular biology and function of the sarcoglycan complex. This review discusses the role of the sarcoglycan complex in skeletal muscle and describes the functional deficiencies that lead to muscular dystrophies.