Disease relevance of Cav2

• C57BL/6 mice were infected with recombinant human caveolin-1 and caveolin-2 adenoviruses [1].

High impact information on Cav2

• In addition, caveolin-2 was retained in the Golgi apparatus in cav1-KD MDCK cells [2].
• Caveolin-2 is a member of the caveolin gene family with no known function [3].
• Caveolin-2-deficient mice show evidence of severe pulmonary dysfunction without disruption of caveolae [3].
• In the absence of caveolin-2 protein expression, caveolae still form and caveolin-1 maintains its localization in plasma membrane caveolae, although in certain tissues caveolin-1 is partially destabilized and shows modestly diminished protein levels [3].
• Despite an intact caveolar membrane system, the Cav-2-null lung parenchyma shows hypercellularity, with thickened alveolar septa and an increase in the number of endothelial cells [3].

Biological context of Cav2

• Interestingly, these Cav-2-null phenotypes are identical to the ones we and others have recently reported for Cav-1-null mice [3].
• We also demonstrate that (i) insulin-stimulation of adipocytes and (ii) integrin ligation of endothelial cells can both induce the tyrosine phosphorylation of caveolin-2 (Tyr(P)(19)) [4].
• With electrophysiology, and using subtype-specific Cav2 channel-blocking toxins, we assessed a possible compensatory contribution of non-Cav2.1 channels to evoked acetylcholine (ACh) release at Tg NMJs [5].

Anatomical context of Cav2

• Thus, Cav-2((-/-)) mice represent a novel animal model-and the first genetically well-defined mouse model-that can be used to study the pathogenesis of tubular aggregate formation, which remains a poorly understood age-related skeletal muscle abnormality [6].
• Finally, because Cav-1 and Cav-2 were not expressed within mature skeletal myofibers, our results indicate that development of these abnormalities probably originates in stem/precursor cells, such as satellite cells or myoblasts [6].
• Furthermore, our co-immunoprecipitation experiments show that caveolin-2 and Ras-GAP are constitutively associated in c-Src expressing NIH-3T3 cells, but not in untransfected NIH-3T3 cells [4].
• In the present study, confocal laser scanning microscopy experiments utilizing both immunofluorescence and green fluorescent protein-labeled Group V PLA2 shows that chronic exposure of the macrophages to lipopolysaccharide results in Group V PLA2 being associated with caveolin-2-containing granules close to the perinuclear region [7].
• We therefore examined caveolin-1 and caveolin-2 expression in resident and thioglycollate-elicited mouse peritoneal macrophages (tg-MPM) and in the J774 mouse macrophage cell line by RT-PCR, ribonuclease protection assay, immunoblotting, and immunofluorescence [8].

Associations of Cav2 with chemical compounds

• Stimulation of cholesterol efflux by HDL(3) leads to caveolin-1 and caveolin-2 secretion to the cell culture medium, a process not detected in the absence of HDL(3) [8].
• Recombinant expression of these mutants in Cos-7 cells demonstrated that neither tyrosine is the unique phosphorylation site, and that double mutation of tyrosines 19 and 27 to alanine abrogates Cav-2 tyrosine phosphorylation [9].
• The experiments of immuno-precipitation showed complex formation between the HO-1 and caveolin-1 or caveolin-2 in the Cd treated MMCs [10].
• Caveolae rich membranous fractions from the MMCs treated with Cd or SPER/NO contained both HO-1 and caveolin-1 or caveolin-2 [10].

Physical interactions of Cav2

• Thus it remains controversial whether caveolin-2 interacts with caveolin-3 [11].

Other interactions of Cav2

• Three SH2 domain-containing proteins, c-Src, Nck, and Ras-GAP, were found to associate with Cav-2 in a phosphorylation-dependent manner [9].
• Recombinant expression of caveolin-2 under the same conditions failed to drive the formation of vesicles, while caveolin-3 expression yielded caveolae-sized vesicles [12].

Analytical, diagnostic and therapeutic context of Cav2

• Both immunoblot analysis and immunohistochemistry dramatically show that Cav-1 and Cav-2 expression is downregulated to almost undetectable levels in the lungs of post-MI rats [13].

References