The caveolin proteins

Abstract

The caveolin gene family has three members in vertebrates: caveolin-1, caveolin-2, and caveolin-3. So far, most caveolin-related research has been conducted in mammals, but the proteins have also been found in other animals, including Xenopus laevis, Fugu rubripes, and Caenorhabditis elegans. Caveolins can serve as protein markers of caveolae ('little caves'), invaginations in the plasma membrane 50-100 nanometers in diameter. Caveolins are found predominantly at the plasma membrane but also in the Golgi, the endoplasmic reticulum, in vesicles, and at cytosolic locations. They are expressed ubiquitously in mammals, but their expression levels vary considerably between tissues. The highest levels of caveolin-1 (also called caveolin, Cav-1 and VIP2I) are found in terminally-differentiated cell types, such as adipocytes, endothelia, smooth muscle cells, and type I pneumocytes. Caveolin-2 (Cav-2) is colocalized and coexpressed with Cav-1 and requires Cav-1 for proper membrane targeting; the Cav-2 gene also maps to the same chromosomal region as Cav-1 (7q31.1 in humans). Caveolin-3 (Cav-3) has greater protein-sequence similarity to Cav-1 than to Cav-2, but it is expressed mainly in muscle cells, including smooth, skeletal, and cardiac myocytes. Caveolins participate in many important cellular processes, including vesicular transport, cholesterol homeostasis, signal transduction, and tumor suppression.

Figure 1

A phylogenetic tree depicting the evolutionary relationships of all known caveolin protein sequences. Note that C. elegans Cav-2 was not included in this analysis because of its low similarity to the mammalian caveolins. GenBank-derived protein sequences were entered into the ClustalW program to generate a phylogenetic tree using the neighbor-joining method. Numbers indicate horizontal branch lengths, which correspond to the estimated evolutionary distances between the protein sequences.

Figure 2

Primary structure and topology of Cav-1. (a) The predicted membrane topology of Cav-1. Two caveolin-1 monomers are shown forming a dimer for simplicity, but about 14-16 monomers normally self-associate to form a single caveolin homo-oligomer (the caveolar assembly unit, akin to the clathrin triskelion). Note that both the amino- and carboxy-terminal domains are oriented towards the cytosolic face of the plasma membrane, with a hairpin loop structure inserted within the membrane bilayer. Modified from Razani et al. [42]. (b) The domains present in Cav-1. Note that the amino-terminal membrane-attachment domain is also called the caveolin scaffolding domain (CSD).