Impairment of caveolae formation and T-system disorganization in human muscular dystrophy with caveolin-3 deficiency.
Caveolin-3, a muscle specific caveolin-related protein, is the principal structural protein of caveolar membranes. We have recently identified an autosomal dominant form of limb girdle muscular dystrophy (LGMD-1C) that is due to caveolin-3 deficiency and caveolin-3 gene mutations. Here, we studied by electron microscopy, including freeze-fracture and lanthanum staining, the distribution of caveolae and the organization of the T-tubule system in caveolin-3 deficient human muscle fibers. We found a severe impairment of caveolae formation at the muscle cell surface, demonstrating that caveolin-3 is essential for the formation and organization of caveolae in muscle fibers. In addition, we also detected a striking disorganization of the T-system openings at the sub-sarcolemmal level in LGMD-1C muscle fibers. These observations provide new perspectives in our understanding of the role of caveolin-3 in muscle and of the pathogenesis of muscle weakness in caveolin-3 deficient muscle.
Minetti
Carlo
C
Servizio Malattie Neuro-Muscolari, Dipartimento di Pediatria, Università di Genova, Istituto G. Gaslini, Genova, Italy. minettic@unige.it
Bado
Massimo
M
Broda
Paolo
P
Sotgia
Federica
F
Bruno
Claudio
C
Galbiati
Ferruccio
F
Volonte
Daniela
D
Lucania
Giuseppe
G
Pavan
Antonio
A
Bonilla
Eduardo
E
Lisanti
Michael P
MP
Cordone
Giuseppe
G
D000293:Adolescent; D021941:Caveolae / Q000502:physiology* / Q000648:ultrastructure; D051244:Caveolin 3; D022461:Caveolins / Q000172:deficiency*; D002648:Child; D005614:Freeze Fracturing; D006801:Humans; D007150:Immunohistochemistry; D007811:Lanthanum; D008854:Microscopy, Electron; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000648:ultrastructure*; D009136:Muscular Dystrophies / Q000378:metabolism* / Q000473:pathology*; D013194:Staining and Labeling
D051244:Caveolin 3; D022461:Caveolins; D007811:Lanthanum