Caveolin

Caveolins are a family of integral membrane proteins that are the principal components of caveolae membranes and involved in receptor-independent endocytosis. Caveolins may act as scaffolding proteins within caveolar membranes by compartmentalizing and concentrating signaling molecules. Various classes of signaling molecules, including G-protein subunits, receptor and non-receptor tyrosine kinases, endothelial nitric oxide synthase (eNOS), and small GTPases, bind Cav-1 through its 'caveolin-scaffolding domain'.

The caveolin gene family has three members in vertebrates: CAV1, CAV2, and CAV3, coding for the proteins caveolin-1, caveolin-2, and caveolin-3, respectively. All three members are membrane proteins with similar structure. Caveolin forms oligomers and associates with cholesterol and sphingolipids in certain areas of the cell membrane, leading to the formation of caveolae.

Structure and expression

The caveolins are similar in structure. They all form hairpin loops that are inserted into the cell membrane. Both the C-terminus and the N-terminus face the cytoplasmic side of the membrane. There are two isoforms of caveolin-1: caveolin-1α and caveolin-1β, the latter lacking a part of the N-terminus.

Caveolin 1

Caveolin-1 is a protein that in humans is encoded by the CAV1 gene.

The scaffolding protein encoded by this gene is the main component of the caveolae plasma membranes found in most cell types. The protein links integrin subunits to the tyrosine kinase FYN, an initiating step in coupling integrins to the Ras-ERK pathway and promoting cell cycle progression. The gene is a tumor suppressor gene candidate and a negative regulator of the Ras-p42/44 MAP kinase cascade. CAV1 and CAV2 are located next to each other on chromosome 7 and express colocalizing proteins that form a stable hetero-oligomeric complex. By using alternative initiation codons in the same reading frame, two isoforms (alpha and beta) are encoded by a single transcript from this gene.

Interactions

Caveolin 1 has been shown to interact with heterotrimeric G proteins, Src tyrosine kinases (Src, Lyn) and H-Ras,cholesterol,TGF beta receptor 1,Endothelial NOS,Androgen receptor,Amyloid precursor protein,Gap junction protein, alpha 1,Nitric oxide synthase 2A,Epidermal growth factor receptor,Endothelin receptor type B,PDGFRB,PDGFRA,PTGS2,TRAF2,Estrogen receptor alpha,Caveolin 2,PLD2,Bruton's tyrosine kinase and SCP2. All these interactions are through a caveolin-scaffolding domain (CSD) within caveolin-1 molecule. Molecules that interact with caveolin-1 contain caveolin-binding motifs (CBM).

Caveolin 2

Caveolin-2 is a protein that in humans is encoded by the CAV2 gene.

The protein encoded by this gene is a major component of the inner surface of caveolae, small invaginations of the plasma membrane, and is involved in essential cellular functions, including signal transduction, lipid metabolism, cellular growth control and apoptosis. This protein may function as a tumor suppressor. CAV1 and CAV2 are located next to each other on chromosome 7 and express colocalizing proteins that form a stable hetero-oligomeric complex. Two transcript variants encoding distinct isoforms have been identified for this gene. By using alternative initiation codons in the same reading frame, two isoforms (alpha and beta) are encoded by one transcript.

Interactions

Caveolin 2 has been shown to interact with Caveolin 1 and RAS p21 protein activator 1.

References

Further reading