Caveolin-deficient mice: insights into caveolar function human disease

In the past several decades, the discovery and detailed characterization of the various subcellular organelles has revealed the intricate workings of the cell. It is of great interest then, that one of the most prominent structures at the plasma membrane, the caveola, has remained the most enigmatic organelle found in cells. Together with their marker proteins, the caveolins, caveolae are present in large numbers in a variety of cell types. Although they were initially proposed to act as mere conduits for cellular uptake, akin to clathrin-coated vesicles, it is now clear that caveolae and caveolins have pleiotropic functions that modulate numerous cellular processes. Many proposed physiological roles for caveolae are controversial, making a rigorous analysis of their function imperative. A giant leap in this regard is the recent series of reports on the phenotypic characterization of caveolin-deficient mice. As loss of caveolin expression causes a concomitant loss in morphologically identifiable caveolae, such animals allow for the first definitive studies of the role of these organelles in various cells in vivo. In this review, we will discuss the known and proposed functions of caveolae in the context of these caveolin-deficient animal models, give a synopsis of the rapidly emerging themes in the field, and discuss the relevance of caveolae to the understanding of human disease.