caveolin1

Caveolin-1, encoded by the CAV1 gene, is a principal scaffolding protein of caveolae, small flask-shaped invaginations of the plasma membrane that are enriched in cholesterol and sphingolipids. It plays a central role in organizing and regulating signaling pathways, endocytosis, and lipid homeostasis in a variety of cell types.

Genetics and structure: The human CAV1 gene is located on chromosome 7q31.2. The caveolin-1 protein is a ~178‑amino-acid integral membrane protein that inserts into the inner leaflet of the plasma membrane with a hairpin-like conformation, assembling into oligomers to form the caveolar coat. Post-translational modifications, including palmitoylation of conserved cysteine residues and phosphorylation at Tyr14, regulate its localization and function.

Function and interactions: The N-terminal region contains a caveolin scaffolding domain that binds a range of signaling proteins, such as Src family kinases, G proteins, and endothelial nitric oxide synthase (eNOS), thereby organizing signaling microdomains. Caveolin-1 associates with cholesterol-rich lipid rafts and participates in cholesterol homeostasis, endocytosis and transcytosis, and mechanotransduction. It forms homo-oligomers and can interact with caveolin-2 to contribute to caveolae structure and dynamics.

Clinical significance: Caveolin-1 has complex, context-dependent roles in disease. Altered Cav1 expression has been observed in cancer, where it can act as a tumor suppressor in some contexts and as a promoter in others. It is also implicated in vascular, metabolic, and fibrotic conditions, and animal models lacking Cav1 show developmental and tissue-specific abnormalities, including lung and adipose tissue defects.