Caveolin 3

Protein coding gene in the species Homo sapiens

Caveolin 3 is a protein that in humans is encoded by the CAV3 gene. Alternative splicing has been identified for this locus, with inclusion or exclusion of a differentially spliced intron. In addition, transcripts utilize multiple polyA sites and contain two potential translation initiation sites.

This gene encodes a caveolin family member, which functions as a component of the caveolae plasma membranes found in most cell types. Caveolin proteins are proposed to be scaffolding proteins for organizing and concentrating certain caveolin interacting molecules.

Using transmission electron microscopy and single particle analysis methods, it has been shown that nine Caveolin 3 monomers assemble to form a complex that is toroidal in shape, ~16.5 nm in diameter and ~5.5 nm in height.

Caveolin 3 is one of three isoforms of the protein caveolin. Caveolin 3 is concentrated in the caveolae of myocytes, and modulates numerous metabolic processes including: nitric oxide synthesis, cholesterol metabolism, and cardiac myocytes contraction. There are many proteins that associate with caveolin 3, including ion channels and exchangers.

In cardiac myocytes, caveolin 3 negatively regulates ATP dependent potassium channels (KATP) localized in caveolae. This association occurs predominately in areas proximate to the peripheral membrane of cardiac myocytes. Normal caveolin 3 expression under conditions of stress increases cardiac cellular levels of ANP, maintaining cardiac homeostasis. Mutations have been identified in the caveolin 3 gene that result in cardiomyopathies. Several of these mutations influence caveolin 3 function by reducing the expression of its cell surface domains. Mutations resulting in loss of function of caveolin 3 cause cardiac myocyte hypertrophy, dilation of the heart, and depression of fractional shortening. Knockout of caveolin 3 genes are sufficient to induce these manifestations. Similarly, dominant negative genotypes for caveolin 3 increase cardiac hypertrophy, whereas increased expression of caveolin 3 inhibits the ability of the heart to hypertrophy, implicating caveolin 3 as a negative regulator of cardiac hypertrophy. Overexpression of caveolin 3 leads to the development of cardiomyopathy, resulting in degeneration of cardiac tissue and manifesting pathologies due to the associated degeneration.