Caveolae, caveolins, and cavins: complex control of cellular signalling and inflammation

Abstract

Caveolae are specialized lipid rafts that form flask-shaped invaginations of the plasma membrane. They are involved in cell signalling and transport and have been shown critically regulate vascular reactivity and blood pressure. The organization and functions of caveolae are mediated by coat proteins (caveolins) and support or adapter proteins (cavins). The caveolins, caveolin-1, -2, and -3, form the structural backbone of caveolae. These proteins are also highly integrated into caveolae function and have their own activity independent of caveolae. The cavins, cavins 1-4, are involved in regulation of caveolae and modulate the function of caveolins by promoting the membrane remodelling and trafficking of caveolin-derived structures. The relationships between these different proteins are complex and intersect with many aspects of cell function. Caveolae have also been implicated in chronic inflammatory conditions and other pathologies including atherosclerosis, inflammatory bowel disease, muscular dystrophy, and generalized dyslipidaemia. The pathogenic role of the caveolins is an emerging area, however, the roles of cavins in disease is just beginning to be explored. This review will examine the relationship between caveolins and cavins and explore the role of caveolae in inflammatory signalling mechanisms.

Figure 1

Dynamic roles of the cavins in determining caveolae structure. Cav-1 and Cav-2 (light blue and green lines) dimerize to form the backbone of caveolae. Cavins as supports proteins then determine the final shape of this structure. Cavin-1 (red circle) directs formation of normal flask-shaped caveolae alone and through interactions with cavin-2 (combined red and yellow circles). Cavin-2 when expressed at higher levels than cavin-1 causes the formation of elongated caveolae which may be involved in channel formation. Finally, cavin-3 (blue circles) directs vesicle formation by caveolae. Dark lines show cytoskeletal components which are thought to mediate the interaction between cavins and caveolins.