title: Caveolin-3 is not an integral component of the dystrophin glycoprotein complex.
abstract: The 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.
authors.affiliation: Howard Hughes Medical Institute, Department of Physiology and Biophysics, University of Iowa College of Medicine, Iowa City 52242, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Crosbie
authors.forename: H
authors.initials: H
authors.lastname: Yamada
authors.forename: D P
authors.initials: DP
authors.lastname: Venzke
authors.forename: M P
authors.initials: MP
authors.lastname: Lisanti
authors.forename: K P
authors.initials: KP
authors.lastname: Campbell
mesh_terms: D000818:Animals; D051244:Caveolin 3; D022461:Caveolins; D002846:Chromatography, Affinity / Q000379:methods; D003598:Cytoskeletal Proteins / Q000032:analysis; D049030:Dystroglycans; D016189:Dystrophin / Q000032:analysis / Q000737:chemistry*; D006801:Humans; D007797:Laminin; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000032:analysis / Q000737:chemistry*; D008565:Membrane Proteins / Q000032:analysis*; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000737:chemistry; D009136:Muscular Dystrophies; D011817:Rabbits; D012508:Sarcolemma / Q000737:chemistry
chemical_list: C495548:Cav3 protein, mouse; D051244:Caveolin 3; D022461:Caveolins; D003598:Cytoskeletal Proteins; C483081:DAG1 protein, human; D016189:Dystrophin; D007797:Laminin; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D049030:Dystroglycans