Impairment of caveolae formation and T-system disorganization in human muscular dystrophy with caveolin-3 deficiency.

Abstract

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.

• Authors: Carlo Minetti, Massimo Bado, Paolo Broda, Federica Sotgia, Claudio Bruno, Ferruccio Galbiati, Daniela Volonte, Giuseppe Lucania, Antonio Pavan, Eduardo Bonilla, Michael P Lisanti, Giuseppe Cordone
• Journal: The American journal of pathology (Am J Pathol) Vol. 160 Issue 1 Pg. 265-70 (Jan 2002) ISSN: 0002-9440 [Print] United States
• PMID: 11786420 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Caveolin 3
• Caveolins
• Lanthanum

Topics

• Adolescent
• Caveolae (physiology, ultrastructure)
• Caveolin 3
• Caveolins (deficiency)
• Child
• Freeze Fracturing
• Humans
• Immunohistochemistry
• Lanthanum
• Microscopy, Electron
• Middle Aged
• Muscle, Skeletal (ultrastructure)
• Muscular Dystrophies (metabolism, pathology)
• Staining and Labeling