AHA-Circ. Research

It is now established that specialized plasmalemmal lipid microenvironments, termed lipid rafts by Simons and Toomre,1 take part in various signal transduction processes. One subset of lipid rafts (which contain mostly cholesterol and sphingolipids) is found in plasmalemmal vesicles termed caveolae. The term caveolae (“little caves”) was introduced more than 40 years ago to describe plasma membrane invaginations identified by electron microscopy in a wide variety of cell types. Originally, these 50to 100-nm plasmalemmal vesicles were shown to participate in the transcellular transport of macromolecules (transcytosis) and in the uptake of small molecules (potocytosis).2 However, it is only recently, with the identification of caveolins as the structural coat component of caveolae, that it has been recognized that caveolae are involved in signal transduction by ensuring the compartmentation of signaling molecules, such as G protein and tyrosine kinase–associated receptors, as well as endothelial nitric oxide synthase (eNOS). The identification of such distinct roles raises the question of how the same organelle can participate in these apparently quite different functions simultaneously. However, in the case of eNOS, recent data suggest that both of these functions (ie, as signaling platforms and intracellular trafficking modules) are, in fact, intimately related and complementary.