Molecular Cloning of Caveolin-3, a Novel Member of the Caveolin Gene Family Expressed Predominantly in Muscle

Abstract

Caveolin, a 21-24-kDa integral membrane protein, is a principal component of caveolar membranes in vivo. Caveolin interacts directly with heterotrimeric G-proteins and can functionally regulate their activity. Recently, a second caveolin gene has been identified and termed caveolin-2. Here, we report the molecular cloning and expression of a third member of the caveolin gene gamily, caveolin-3. Caveolin-3 is most closely related to caveolin-1 based on protein sequence homology; caveolin-1 and caveolin-3 are approximately 65% identical and approximately 85% similar. A single stretch of eight amino acids (FED-VIAEP) is identical in caveolin-1, -2, and -3. This conserved region may represent a "caveolin signature sequence" that is characteristic of members of the caveolin gene family. Caveolin-3 mRNA is expressed predominantly in muscle tissue-types (skeletal muscle, diaphragm, and heart) and is selectively induced during the differentiation of skeletal C2C12 myoblasts in culture. In many respects, caveolin-3 is similar to caveolin-1: (i) caveolin-3 migrates in velocity gradients as a high molecular mass complex; (ii) caveolin-3 colocalizes with caveolin-1 by immunofluorescence microscopy and cell fractionation studies; and (iii) a caveolin-3-derived polypeptide functionally suppresses the basal GTPase activity of purified heterotrimeric G-proteins. Identification of a muscle-specific member of the caveolin gene family may have implications for understanding the role of caveolin in different muscle cell types (smooth, cardiac, and skeletal) as previous morphological studies have demonstrated that caveolae are abundant in these cells. Our results also suggest that other as yet unknown caveolin family members are likely to exist and may be expressed in a regulated or tissue-specific fashion.

Caveolin proteins and estrogen signaling in the brain

“…Caveolae were first recognized in epithelial cells by electron micrograph techniques over 50 years ago [25]. There are three known caveolin proteins, caveolin 1 (CAV1, with splice variants α and β), caveolin 2 (CAV2), and caveolin 3 (CAV3) [26][27][28]. CAV1 and CAV2 have overlapping expression patterns in a variety of cell types including, neurons and glia [29,30], endothelial [31], and epithelial cells [32].…”

“…In comparison, knockout of either CAV1 or CAV3 results in a loss of caveolae formations in the specific cell type for which they are expressed [35,36]. Notably, it was originally believed that expression of CAV3 was restricted to skeletal and smooth muscle cells [26,[37][38][39]. We now know this not to be the case, as expression of CAV3 is more widespread, including its presence in nervous tissue [30].…”

And still they are moving… Dynamic properties of caveolae

“…Recently two homologues of the protein have been identified [29][30][31], with one of these homologues being expressed exclusively in muscle [29,31]. In this review for the sake of simplicity, caveolin-1 will be used instead of VIP21-caveolin (see [41]).…”

Analysis of the CAVEOLIN-1 gene at human chromosome 7q31.1 in primary tumours and tumour-derived cell lines

“…Recently, a family of caveolin-related proteins have been identi®ed , Tang et al, 1996 and caveolin has been re-named caveolin-1. Here, we report the mapping of the gene encoding Caveolin-1 to human chromosome 7q31, in proximity to the marker D7S522, which has been mapped to q31.1.…”