Caveolin regulation of endothelial function

Departments of 1 Pharmacology and 2 Anesthesiology, University of Illinois-Chicago Medical Center, Chicago, Illinois 60612; 3 Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536; 4 Department of Cellular and Molecular Medicine, University of California-San Diego, La Jolla, California 92093-0651; and 5 Department of Cell Biology, University of Texas Southwest Medical Center, Dallas, Texas 75235-9039 Caveolae are the sites in the cell membrane responsible for concentrating an array of signaling molecules critical for cell function. Recent studies have begun to identify the functions of caveolin-1, the 22-kDa caveolar protein that oligomerizes and inserts into the cytoplasmic face of the plasma membrane. Caveolin-1 appears to regulate caveolar internalization by stabilizing caveolae at the plasma membrane rather than controlling the shape of the membrane invagination. Because caveolin-1 is a scaffolding protein, it has also been hypothesized to function as a "master regulator" of signaling molecules in caveolae. Deletion of the caveolin-1 gene in mice resulted in cardiac hypertrophy and lung fibrosis, indicating its importance in cardiac and lung development. In the endothelium, caveolin-1 regulates nitric oxide signaling by binding to and inhibiting endothelial nitric oxide synthase (eNOS). Increased cytosolic Ca 2+ or activation of the kinase Akt leads to eNOS activation and its dissociation from caveolin-1. Caveolae have also been proposed as the vesicle carriers responsible for transcellular transport (transcytosis) in endothelial cells. Transcytosis, the primary means of albumin transport across continuous endothelia, occurs by fission of caveolae from the membrane. This event is regulated by tyrosine phosphorylation of caveolin-1 and dynamin. As Ca 2+ influx channels and pumps are localized in caveolae, caveolin-1 is also an important determinant of Ca 2+ signaling in endothelial cells. Many of these findings were presented in San Diego, CA, at the 2003 Experimental Biology symposium "Caveolin Regulation of Endothelial Function" and are reviewed in this summary. caveolae; Src ; dynamin; endothelial nitric oxide synthase; CAV1 knockout; calcium; lipid raft domains Address for reprint requests and other correspondence: Asrar B. Malik, Dept. of Pharmacology, Univ. of Illinois at Chicago, 835 S. Wolcott Ave. (m/c 868), Chicago, IL 60612 (E-mail: abmalik{at}uic.edu ).