Caveolae, caveolins, cavins, and endothelial cell function: new insights

Abstract

Caveolae are cholesterol and glycosphingolipid-rich flask-shaped invaginations of the plasma membrane which are particularly abundant in vascular endothelium and present in all other cell types of the cardiovascular system, including vascular smooth-muscle cells, macrophages, cardiac myocytes, and fibroblasts. Caveolins and the more recently discovered cavins are the major protein components of caveolae. When caveolae were discovered, their functional role was believed to be limited to transport across the endothelial cell barrier. Since then, however, a large body of evidence has accumulated, suggesting that these microdomains are very important in regulating many other important endothelial cell functions, mostly due to their ability to concentrate and compartmentalize various signaling molecules. Over the course of several years, multiple studies involving knockout mouse and small interfering RNA approaches have considerably enhanced our understanding of the role of caveolae and caveolin-1 in regulating many cardiovascular functions. New findings have been reported implicating other caveolar protein components in endothelial cell signaling and function, such as the understudied caveolin-2 and newly discovered cavin proteins. The aim of this review is to focus primarily on molecular and cellular aspects of the role of caveolae, caveolins, and cavins in endothelial cell signaling and function. In addition, where appropriate, the possible implications for the cardiovascular and pulmonary physiology and pathophysiology will be discussed.

Heparin Decreases in Tumor Necrosis Factor α (TNFα)-induced Endothelial Stress Responses Require Transmembrane Protein 184A and Induction of Dual Specificity Phosphatase 1

“…Caveolae organize numerous players in signaling pathways (54). The role of caveolae in endothelial nitrous oxide synthase activation, which results in increased NO production and resultant increases in cGMP (55), and the colocalization of the heparin receptor with caveolin-1 (28) suggest that these players could be linked in modulating healthy endothelial function.…”

Increased PDE5 activity and decreased Rho kinase and PKC activities in colonic muscle from caveolin-1−/− mice impair the peristaltic reflex and propulsion

“…Caveolins are a key component of the caveolae in smooth muscle, which act to regulate many major membrane functions, including organizing cell signaling components and vesicular trafficking (18,35,36,55). They have been shown to participate in excitation-contraction coupling in gut, vascular, and airway smooth muscle, but they have also been shown to have a role in the controlling relaxation pathways, particularly those involving NO (2,4,20,37,46,50).…”

Megalencephalic leukoencephalopathy with cysts: theGlialcam‐null mouse model

“…Immunogold electron microscopy shows that GlialCAM and MLC1 co‐localize in astrocyte–astrocyte junctions at astrocytic endfeet 13. Both MLC1 and GlialCAM are associated with caveolae, which are important in compartmentalization of components involved in signal transduction, transport functions, endocytosis, and transcytosis 20, 21, 22, 23…”