Caveolins

Caveolins are a family of integral membrane proteins that are essential components of caveolae, small flask-shaped invaginations of the plasma membrane found in many cell types. The vertebrate family comprises three members: caveolin-1 (Cav-1), caveolin-2 (Cav-2) and caveolin-3 (Cav-3). Cav-1 and Cav-2 are widely expressed, whereas Cav-3 is predominantly expressed in skeletal and cardiac muscle.

Caveolins share a central scaffolding domain and a caveolin signature motif, and they form high-molecular-weight oligomers that assemble into caveolae together with other structural proteins called cavins. The caveolar coat includes Cav-1/Cav-2 oligomers and cavin family proteins (such as PTRF/Cavin1, SDPR/Cavin2, and PRKCDBP/Cavin3). Caveolins also bind cholesterol and associate with cholesterol-rich membrane microdomains, contributing to membrane curvature and stability.

Functions attributed to caveolins include organizing and regulating signaling pathways at the plasma membrane, endocytosis via caveolae, and lipid and cholesterol homeostasis. Cav-1, in particular, modulates endothelial nitric oxide synthase (eNOS) activity, and caveolae participate in mechanotransduction and insulin signaling. Cav-1 and Cav-2 can influence various receptor-mediated pathways, while Cav-3 is important for muscle membrane integrity and signaling in cardiac and skeletal muscle.

Genetic and expression changes in caveolins have clinical relevance. Mutations in CAV3 cause muscular dystrophies such as limb-girdle muscular dystrophy type 1C and rippling muscle disease. Altered CAV1 expression is linked to lipodystrophy and pulmonary arterial hypertension, among other conditions. In general, caveolins are studied as key components of caveolae and as regulators of diverse cellular signaling networks.