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.