Molecular Composition and Ultrastructure of the Caveolar Coat Complex

Abstract

Author SummaryCaveolae are flask-shaped invaginations in the plasma membrane of many mammalian cell types, and are particularly abundant in fat cells, muscle cells, and the cells that line blood vessels. Although caveolae are likely to be important for cellular responses to mechanical stress, intracellular trafficking, and signaling events, we still lack an understanding of the precise molecular mechanisms for how they form and carry out these functions. Here we address the question of how caveolae are made. Recent years have seen a considerable expansion of the catalogue of known protein components present in caveolae. Our study shows that the main protein components, cavins and caveolins, assemble into one specific complex. We reveal how different amounts of two caveolar proteins, cavin 2 and cavin 3, may be incorporated into this single type of complex, thereby potentially conferring different functional properties on caveolae. Using electron microscopy, we demonstrate that the protein complex is distributed all around the membrane bulb of caveolae, and so can be truly described as the caveolar coat. The caveolar coat excludes the protein EHD2, which regulates the dynamics of caveolae—this protein has a distinct distribution at the caveolar neck. These findings provide the basis for a more complete understanding of the network of protein interactions that produces caveolae.