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(American Journal of Pathology. 2002;160:265-270.)
© 2002 American Society for Investigative Pathology

Regular Articles

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

Carlo Minetti^*, Massimo Bado^*, Paolo Broda^*, Federica Sotgia^*, Claudio Bruno^*, Ferruccio Galbiati, Daniela Volonte, Giuseppe Lucania, Antonio Pavan, Eduardo Bonilla^¶, Michael P. Lisanti and Giuseppe Cordone^*

From the Servizio Malattie Neuro-Muscolari,^*
Dipartimento di Pediatria, Università di Genova, Istituto G. Gaslini, Genova, Italy; Department of Molecular Pharmacology,
Albert Einstein College of Medicine, Bronx, New York; Dipartimento di Medicina Sperimentale e Patologia,
Università di Roma "La Sapienza," Roma, Italy; Dipartimento di Medicina Sperimentale,
Università dell’ Aquila, L’Aquila, Italy; Departments of Neurology and Pathology,^¶
Columbia University, New York, New York

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.

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