Caveolin-3 is not an integral component of the dystrophin glycoprotein complex

AbstractThe dystrophin-glycoprotein complex is a multi-subunit protein complex that spans the muscle plasma membrane (sarcolemma) and forms a link between the intracellular cytoskeleton and the extracellular matrix. Caveolin-3, the muscle specific form of caveolin, is also a major structural and regulatory integral membrane protein found at the sarcolemma. Oligomers of caveolin-3 form the structural framework for small membrane pockets known as caveolae. We directly examined whether caveolin-3 is an integral component of the dystrophin-glycoprotein complex by examining four common biochemical and cellular properties of proteins integrally bound to the dystrophin-glycoprotein complex. We found that caveolin-3 de-enriches with partial purification of the dystrophin-glycoprotein complex although a small amount of caveolin-3 is present. Sucrose gradient fractionation and laminin affinity chromatography completely separate this residual caveolin-3 from the core components of the dystrophin-glycoprotein complex. We also show that caveolin-3 expression at the sarcolemma is not reduced in patients with primary mutations in either dystrophin or the sarcoglycans. This data demonstrates that localization of caveolin-3 to the sarcolemma occurs independently of the dystrophin-glycoprotein complex and that caveolin-3 is not an integral component of the dystrophin-glycoprotein complex