Caveolin-3 in muscular dystrophy.
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.
McNally
E M
EM
Division of Genetics and the Howard Hughes Medical Institute, Children's Hospital, Boston, MA 02115, USA. emcnally@medicine.bsd.uchicago.edu
de Sá Moreira
E
E
Duggan
D J
DJ
Bönnemann
C G
CG
Lisanti
M P
MP
Lidov
H G
HG
Vainzof
M
M
Passos-Bueno
M R
MR
Hoffman
E P
EP
Zatz
M
M
Kunkel
L M
LM
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
C495548:Cav3 protein, mouse; C495549:Cav3 protein, rat; D051244:Caveolin 3; D022461:Caveolins; D016189:Dystrophin; D008565:Membrane Proteins; D009124:Muscle Proteins