Caveolina

Caveolins are a family of integral membrane proteins that are the principal components of caveolae, which are small, flask-shaped invaginations of the plasma membrane found in many vertebrate cell types. In mammals, the three main isoforms are caveolin-1 (Cav-1), caveolin-2 (Cav-2), and caveolin-3 (Cav-3). Cav-1 and Cav-2 are widely expressed in non-muscle cells, whereas Cav-3 is primarily expressed in skeletal and cardiac muscle. Caveolins assemble with cavin proteins to form the caveolar coat that shapes caveolae and organizes signaling platforms at the membrane.

Structure and function: Caveolins are characterized by a hydrophobic membrane-spanning region, a long cytoplasmic tail, and a conserved caveolin scaffolding domain (CSD), roughly residues 82–101 in Cav-1, which binds and modulates multiple signaling proteins, including G-protein subunits and Src family kinases. This arrangement helps regulate signal transduction pathways and lipid metabolism. Caveolae also serve as membrane reservoirs that buffer tension and participate in endocytosis and transcytosis independent of clathrin-mediated routes.

Clinical relevance: Altered expression or function of caveolins is associated with various diseases. Changes in Cav-1 and Cav-2 levels are observed in cancer and metabolic disorders such as obesity and insulin resistance, while Cav-3 mutations can cause muscular dystrophy and related myopathies. Caveolae dysfunction has also been implicated in certain cardiovascular and pulmonary conditions.

Evolution and genetics: Caveolin genes are conserved across vertebrates and contribute to the organization of membrane microdomains that coordinate signaling, trafficking, and lipid homeostasis.