Structure and localizations
Caveolin-1 (Cav1) is a 22 KDa multifunctional scaffolding protein with multiple binding partners that is associated with cell surface caveolae and the regulation of lipid raft domains.
CAV-1 is an integral membrane protein found in caveolae, omega-shaped invaginations of the plasma membrane that form a subdomain of cholesterol- and sphingolipid-rich lipid rafts.Cav1 gene is localized to locus D7S522 of human chromosome 7q31.1In vivo, two isoforms of Cav1 are known to exist: α-caveolin that contains residues 1–178 and β-caveolin that contains residues 32–178. Two other proteins of the same family, Cav2 and Cav3, exist and differ in their patterns of expression in different cell types.
CAV-1 inserts in the plasma membrane by a hairpin domain and by three palmitoyl groups in the C-terminal region; both C-term and N-term face the citoplasm. Two main phosphorylation sites have been localized to positions Ser80 and Tyr14, located near the N-term. The Cav1 scaffolding domain (CSD) is a highly conserved region that encompasses a region situated between D82 and R101; the CSD was found to interact with multiple signalling regulators. This region of Cav1 also contains an amino acid sequence that interacts with cholesterol. Cav1 is a scaffolding protein that oligomerizes at the plasma membrane as a heptameric subunit; indeed, caveolae are stable structures first generated in the Golgi apparatus and their exit from the secretory pathway is associated with Cav1 oligomerization. Cav1, via biogenesis of caveolae, is not only essential for lipid uptake and regulation, transcellular transport and signalling in endothelial cells, but also for the entry of certain viruses into mammalian cells (SV40). Cav1 and its phosphorylation can impact on the domain recruitment of signalling protein partners and consequently contribute to the trafficking of signalling proteins to and from the plasma membrane. Moreover, Cav1 is also localized outside of caveolar regions in the cytoplasm, focal adhesions, the extracellular milieu, and the nucleus emphasizing its function in a variety of cell signalling and mechanotransduction phenomena that may regulate tumor cell behaviour. Some Cav1 has been localized, in a cell type-specific manner, to the cytosol (for example in skeletal muscle cells and keratinocytes), secretory vesicles (in endocrine and exocrine cells), mitochondria (in airway epithelial cells) and lipid droplets. Cav1 has also been localized to the nucleus of ovarian carcinoma cells where it binds directly to promoter regions of the cyclin D1 and folate receptor genes. Cav1 nuclear translocation is activated upon vascular endothelial growth factor (VEGF) stimulation and may represent a mechanism for targeting nitric oxide production to the nucleus where it could influence transcription factor activation.
Cav2 is able to form a stable hetero-oligomeric complex with Cav1 but is not essential for caveolae biogenesis, while Cav3 is primarily located in muscle tissues but is also expressed in glial cells and it plays an essential role in caveolae biogenesis in those tissues where it is expressed.