CAVEOLINS

Abstract

Caveolae are small invaginations of the plasma membrane that are implicated in endocytosis, vesicular trafficking, and signal transduction. Caveolin proteins (Cav), the principal structural proteins of caveolae, consist of three distinct genes, namely Cav-1, Cav-2, and Cav-3. Cav-1 and Cav-2 are usually coexpressed and are particularly abundant in endothelial cells, fibroblasts, smooth muscle cells, and epithelial cells. In contrast, Cav-3 is muscle-specific and is solely expressed in smooth, cardiac, and skeletal muscle cells. Caveolin proteins appear to play a role as key regulators of pulmonary structure and function. Homozygous deletion of the Cav-1 gene (Cav-1 (−/−)) results in numerous pulmonary abnormalities, characterized by a loss of Cav-1 and Cav-2 protein expression, a loss of caveolae formation, thickened alveolar septa, lung hypercellularity, pulmonary endothelial cell proliferation, fibrosis, and exercise intolerance. Cav-2 (−/−) mice show similar pulmonary abnormalities to the Cav-1 (−/−) mice, but without a loss of Cav-1 expression and normal caveolae formation. Furthermore, Cav-1 (−/−) mice develop pulmonary hypertension and right ventricular hypertrophy. Interestingly, the endogenous levels of caveolin proteins appear to be altered in numerous pulmonary disorders, such as pulmonary hypertension, lung cancers, pulmonary fibrosis, and pulmonary interstitial edema.