title: Relationships between caveolae and eNOS: everything in proximity and the proximity of everything.
abstract: Caveolae, flask-shaped invaginations of the plasma membrane occupying up to 30% of cell surface in capillaries, represent a predominant location of endothelial nitric oxide synthase (eNOS) in endothelial cells. The caveolar coat protein caveolin forms high-molecular-weight, Triton-insoluble complexes through oligomerization mediated by interactions between NH2-terminal residues 61-101. eNOS is targeted to caveolae by cotranslational N-myristoylation and posttranslational palmitoylation. Caveolin-1 coimmunoprecipitates with eNOS; interaction with eNOS occurs via the caveolin-1 scaffolding domain and appears to result in the inhibition of NOS activity. The inhibitory conformation of eNOS is reversed by the addition of excess Ca2+/calmodulin and by Akt-induced phosphorylation of eNOS. Here, we shall dissect the system using the classic paradigm of a reflex loop: 1) the action of afferent elements, such as fluid shear stress and its putative caveolar sensor, on caveolae; 2) the ways in which afferent signals may affect the central element, the activation of the eNOS-nitric oxide system; and 3) several resultant well-established and novel physiologically important effector mechanisms, i.e., vasorelaxation, angiogenesis, membrane fluidity, endothelial permeability, deterrance of inflammatory cells, and prevention of platelet aggregation.
authors.affiliation: Department of Medicine, State University of New York at Stony Brook, Stony Brook, New York 11794-8152, USA. Michael_Goligorsky@nymc.edu
authors.forename: Michael S
authors.initials: MS
authors.lastname: Goligorsky
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Sergey
authors.initials: S
authors.lastname: Brodsky
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D002196:Capillaries / Q000201:enzymology; D021941:Caveolae / Q000201:enzymology*; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000166:cytology* / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III
chemical_list: C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III