A New Role for Caveolin-1

Abstract

Caveolae was initially described as plasmalemmal vesicles in the endothelium of the heart in the early 1950s. Since then, caveolae have been identified as the 50- to 100-nm flask-shaped invaginations of the plasma membrane in a wide variety of tissues and cell types. In the past decade, a great deal of effort has been expended to determine the biological role of caveolae. Although detailed morphological examinations have provided some insights into their function, it was not until the discovery of the caveolar coat proteins in the early 1990s that the true nature and importance of these organelles were realized. To date, 3 caveolin proteins have been identified and termed as caveolin-1, -2, and -3, possessing molecular masses between 18 and 24 kDa.1 These proteins serve as markers for and are the major components of caveolae, consisting of a hairpin-like structure with both the N and C terminus exposed to the cytoplasm. The N-terminal domain contains a caveolin scaffolding domain (residues 82 to 101), which is essential for the formation of caveolin oligomers and interaction with other proteins. Given their widespread tissue distributions, a number of in vitro and in vivo studies have implicated caveolae and caveolins in the pathogenesis of diabetes mellitus, atherosclerosis, cardiac hypertrophy, heart failure, pulmonary fibrosis, degenerative muscular dystrophies, and cancer.1 The recent generation of caveolin null mice has made it possible to evaluate the significance of each caveolin protein in the context of whole animal physiology and pathology (see Table). View this table: Table. Cardiovascular Phenotypes Observed in Caveolin Knockout Mice As the major coat protein for caveolae assembly, caveolin-1 is particularly abundant in endothelial cells, which are critically involved in the regulation of vascular tone and cardiovascular homeostasis through NO produced by endothelial NO synthase (eNOS). The identification of eNOS localized in plasmalemmal caveolae of endothelial …