Disease relevance of CAV1

• Translocation of caveolin after exposure to oxidized LDL suggests that the localization of caveolin may be a valuable tool to study models of early atherogenesis [1].

High impact information on CAV1

• Caveolae and caveolin-containing detergent-insoluble glycolipid-enriched rafts (DIG) have been implicated to function as plasma membrane microcompartments or domains for the preassembly of signaling complexes, keeping them in the basal inactive state [2].
• This correlates well to increased tyrosine phosphorylation of caveolin and the insulin receptor substrate protein 1 (up to 6- and 15-fold), as well as elevated phosphatidylinositol-3' kinase activity and glucose transport (to up to 7- and 13-fold) [2].
• These data suggest that in adipocytes a subset of signaling components is concentrated at caveolae-DIG via the interaction between their CBD and the CSD of caveolin [2].
• Endothelial nitric-oxide synthase (eNOS) associates with caveolae and is directly regulated by the caveola protein, caveolin [3].
• Cyclodextrin also depleted caveolae of cholesterol and caused eNOS and caveolin to translocate from caveolae [3].

Biological context of CAV1

• Ouabain-induced endocytosis of the plasmalemmal Na/K-ATPase in LLC-PK1 cells requires caveolin-1 [4].
• OBJECTIVE: Cholesterol-rich membrane domains, which contain the scaffold protein caveolin-1 (Cav-1) (caveolae), represent an important structural element involved in endothelial signal transduction [5].
• We conclude that a similar distribution of one pool of PFK with CAV-1 contributes to the compartmentation of glycolysis from gluconeogenesis [6].
• In both phenotypes, CAV-1 fluorescence overlapped with PFK fluorescence (83.1 and 81.5%, respectively) [6].

Anatomical context of CAV1

• We found that treatment with 10 microgram/ml oxLDL for 60 min caused greater than 90% of eNOS and caveolin to leave caveolae [3].
• Immunohistochemistry of porcine pulmonary artery endothelial cells (PAEC) with antibodies specific for caveolin, endothelial nitric-oxide synthase (eNOS), and the arginine transporter (CAT1) demonstrates that all of these proteins co-localize in plasma membrane caveolae [7].
• Involvement of caveolin in ligand-induced recruitment and internalization of A(1) adenosine receptor and adenosine deaminase in an epithelial cell line [8].
• HDL-associated [(14)C]alpha TocH taken up by brain capillary endothelial cells was recovered in sucrose gradient fractions containing the majority of cellular caveolin-1, the major caveolae-associated protein [9].
• Cholesterol depletion with MbetaCD did not disrupt the interaction between cPLA(2) and caveolin-1 but prevented targeting of cPLA(2) to low density membranes [5].

Associations of CAV1 with chemical compounds

• We demonstrated that A(1)R agonist N(6)-(R)-phenylisopropyl adenosine promotes the translocation of A(1)R into low-density gradient fractions containing caveolin [8].
• Instead, we suggest that the ability of LacCer to confer detergent-insolubility on this GPI-anchored protein is dependent on the structure of the lipid molecule in its entirety, and that this glycosphingolipid may have an important role to play in the stabilization of lipid rafts, particularly the caveolin-free glycosphingolipid signalling domains [10].
• CONCLUSION: The integrity of caveolin-1-containing membrane microdomains is prerequisite for arachidonic acid recruitment and EDHF signaling in porcine arteries [5].
• Their lipid composition, 22% SM, 60% cholesterol, 11% phosphatidylethanolamine, 8% PC, <1% phosphatidylinositol, and coisolation with 5'-nucleotidase and caveolin-1 suggest that they are liquid-ordered membranes [11].
• Treatment with methyl-beta-cyclodextrin--a cholesterol chelator--leads to a spreading of both caveolin and completely inactive Ca2+-ATPase toward high-density fractions [12].

Other interactions of CAV1

• Depletion of caveolin-1 also significantly reduced the ouabain-induced accumulation of Na/K-ATPase alpha-1 subunit, EGFR, Src, and MAPKs in clathrin-coat vesicles, as well as early and late endosomes [4].
• NOS-3, HSP90, and caveolin-1 levels were similar in hypoxic and control PAs [13].
• During mass transfer studies using alpha TocH-enriched HDL, approximately 50% of cellular alpha TocH was recovered with the bulk of cellular caveolin-1 and SR-BI [9].
• We show that the GPI-anchored protein membrane dipeptidase is localized in detergent-insoluble lipid rafts isolated from porcine kidney microvillar membranes, and that these rafts, which lack caveolin, are enriched not only in sphingomyelin and cholesterol, but also in the glycosphingolipid lactosylceramide (LacCer) [10].
• Immunoblot and immunohistochemistry results indicate the following: 1) LAD endothelial NOS protein content was similar among groups; 2) HF decreased LAD superoxide dismutase (SOD) but increased caveolin-1 content; and 3) Ex increased SOD content of HF LADs [14].

Analytical, diagnostic and therapeutic context of CAV1

• Cellular localization of caveolin-1 and phospholipase A(2) was investigated by cell fractionation, and interaction of cPLA(2) with caveolin-1 was tested by immunoprecipitation experiments [5].
• Cell fractionation experiments indicated targeting of cPLA(2) to low density, caveolin-1 rich membranes and immunoprecipitation experiments demonstrated association of phospholipase A(2) with the scaffold protein of caveolae, caveolin-1 [5].
• We used confocal microscopy to determine the localization of caveolin-1 (CAV-1) and phosphofructokinase (PFK) in freshly isolated VSM cells and cultured A7r5 cells [6].
• Immunoblotting of lung homogenates from normal and irradiated rats using specific anti-caveolin antibodies confirmed the presence of caveolin in normal tissue and its marked decrease of expression in fibrotic tissue [15].
• Immunofluorescence and immunoblot analyses confirmed the presence of caveolin-1 and caveolin-2 in the lens epithelium [16].

References