MOLECULAR-CLONING OF CAVEOLIN-3, A NOVEL MEMBER OF THE CAVEOLIN GENE FAMILY EXPRESSED PREDOMINANTLY IN MUSCLE

Caveolin, a 21-24-kDa integral membrane protein, is a principal compon ent of caveolar membranes in vivo. Caveolin interacts directly with he terotrimeric G-proteins and can functionally regulate their activity. Recently, a second caveolin gene has been identified and termed caveol in-2. Here, we report the molecular cloning and expression of a third member of the caveolin gene family, caveolin-3. Caveolin-3 is most clo sely related to caveolin-1 based on protein sequence homology; caveoli n-1 and caveolin 3 are similar to 65% identical and similar to 85% sim ilar. A single stretch of eight amino acids (FEDVIAEP) is identical in caveolin-1, -2, and -3. This conserved region may represent a ''caveo lin signature sequence'' that is characteristic of members of the cave olin gene family. Caveolin-3 mRNA is expressed predominantly in muscle tissue types (skeletal muscle, diaphragm, and heart) and is selective ly induced during the differentiation of skeletal C2C12 myoblasts in c ulture. In many respects, caveolin-3 is similar to caveolin-1: (i) cav eolin-3 migrates in velocity gradients as a high molecular mass comple x; (ii) caveolin-3 colocalizes with caveolin-1 by immunofluorescence m icroscopy and cell fractionation studies; and (iii) a caveolin-3-deriv ed polypeptide functionally suppresses the basal GTPase activity of pu rified heterotrimeric G-proteins. Identification of a muscle-specific member of the caveolin gene family may have implications for understan ding the role of caveolin in different muscle cell types (smooth, card iac, and skeletal) as previous morphological studies have demonstrated that caveolae are abundant in these cells. Our results also suggest t hat other as yet unknown caveolin family members are likely to exist a nd may be expressed in a regulated or tissue-specific fashion.