title: Caveolin-3 in muscular dystrophy.
abstract: The dystrophin-glycoprotein complex (DGC) serves as a link between cytoplasmic actin, the membrane and the extracellular matrix of striated muscle. Genetic defects in genes encoding a subset of DGC proteins result in muscular dystrophy and a secondary decrease in other DGC proteins. Caveolae are dynamic structures that have been implicated in a number of functions including endocytosis, potocytosis and signal transduction. Caveolin (VIP-21) is thought to play a structural role in the formation of non-clathrin-coated vesicles in a number of different cell types. Caveolin-3, or M-caveolin, was identified as a muscle-specific form of the caveolin family. We show that caveolin-3 co-purifies with dystrophin, and that a fraction of caveolin-3 is a dystrophin-associated protein. We isolated the gene for human caveolin-3 and mapped it to chromosome 3p25. We determined the genomic organization of human caveolin-3 and devised a screening strategy to look for mutations in caveolin-3 in patients with muscular dystrophy. Of 82 patients screened, two nucleotide changes were found that resulted in amino acid substitutions (G55S and C71W); these changes were not seen in a control population. The amino acid changes map to a functionally important domain in caveolin-3, suggesting that these are not benign polymorphisms and instead are disease-causing mutations.
authors.affiliation: Division of Genetics and the Howard Hughes Medical Institute, Children's Hospital, Boston, MA 02115, USA. emcnally@medicine.bsd.uchicago.edu
authors.forename: E M
authors.initials: EM
authors.lastname: McNally
authors.forename: E
authors.initials: E
authors.lastname: de Sá Moreira
authors.forename: D J
authors.initials: DJ
authors.lastname: Duggan
authors.forename: C G
authors.initials: CG
authors.lastname: Bönnemann
authors.forename: M P
authors.initials: MP
authors.lastname: Lisanti
authors.forename: H G
authors.initials: HG
authors.lastname: Lidov
authors.forename: M
authors.initials: M
authors.lastname: Vainzof
authors.forename: M R
authors.initials: MR
authors.lastname: Passos-Bueno
authors.forename: E P
authors.initials: EP
authors.lastname: Hoffman
authors.forename: M
authors.initials: M
authors.lastname: Zatz
authors.forename: L M
authors.initials: LM
authors.lastname: Kunkel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051244:Caveolin 3; D022461:Caveolins; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D016189:Dystrophin / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism; D051381:Rats
chemical_list: C495548:Cav3 protein, mouse; C495549:Cav3 protein, rat; D051244:Caveolin 3; D022461:Caveolins; D016189:Dystrophin; D008565:Membrane Proteins; D009124:Muscle Proteins