Impairment of Caveolae Formation and T-System Disorganization in Human Muscular Dystrophy with Caveolin-3 Deficiency

• Published in: The American journal of pathology Vol. 160; no. 1; pp. 265 - 270
• Main Authors: Minetti, Carlo, Bado, Massimo, Broda, Paolo, Sotgia, Federica, Bruno, Claudio, Galbiati, Ferruccio, Volonte, Daniela, Lucania, Giuseppe, Pavan, Antonio, Bonilla, Eduardo, Lisanti, Michael P., Cordone, Giuseppe
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 2002; ASIP; American Society for Investigative Pathology
• Subjects: Adolescent; Biological and medical sciences; Caveolae - physiology; Caveolae - ultrastructure; Caveolin 3; Caveolins - deficiency; Child; Diseases of striated muscles. Neuromuscular diseases; Freeze Fracturing; Humans; Immunohistochemistry; Lanthanum; Medical sciences; Microscopy, Electron; Middle Aged; Muscle, Skeletal - ultrastructure; Muscular Dystrophies - metabolism; Muscular Dystrophies - pathology; Neurology; Regular; Staining and Labeling; Human; Immunohistochemistry; Neuromuscular diseases; Nervous system diseases; Pathogenesis; Deficiency; Electron microscopy; Striated muscle; Cell surface; Muscular dystrophy; Genetic disease; Pathology; Image analysis
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)64370-2

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.