Disease relevance of Cav3

• A decrease in caveolin-3 expression may play a role in the development of cardiac hypertrophy in SHR, presumably through de-regulating the inhibition of growth signal in the hearts of SHR in the hypertrophic stage [1].
• Behavior of caveolae and caveolin-3 during the development of myocyte hypertrophy [2].
• Using an experimental model of myocardial infarction (MI) in senescent rats, we demonstrated a significant increase in cardiac NOS1 expression and activity in MI, coupled with the translocation of this enzyme to the sarcolemma through interactions with caveolin-3 [3].

High impact information on Cav3

• Caveolin-1 and -2 show the widest range of expression, whereas caveolin-3 expression is restricted to muscle cell types [4].
• Finally, a minor fraction of a protein that has been designated as a receptor for activated protein kinase C resides in caveolae and (along with caveolin-3) could represent a mechanism to target PKC isoforms to cardiomyocyte caveolae [5].
• Biochemical as well as immunocytochemical studies suggested that the PMCA in large part was colocalized with caveolin 3 in caveolae of cardiomyocytes [6].
• The experiments showed that cellular caveolin-3, a fraction of cellular ANP-RB, and a fraction of cellular ANP colocalize at the plasmalemma of cultured atrial myocytes and of freshly dissociated atrial myocytes [7].
• Using sucrose density fractionation of adult cardiac myocytes, we detected Cav-3 in both buoyant membrane fractions (BF) and heavy/non-buoyant fractions (HF); beta2-adrenergic receptors (AR) in BF; and AC5/6, beta1-AR, M4-muscarinic acetylcholine receptors (mAChR), mu-opioid receptors, and Galpha(s) in both BF and HF [8].

Chemical compound and disease context of Cav3

• Phenylephrine induced cellular hypertrophy associated with an increase of the number of caveolae and an up-regulation of caveolin-3 [2].

Biological context of Cav3

• Caveolin-3 the muscle-specific caveolin isoform, acts like the more ubiquitously expressed caveolin-1 to sculpt caveolae, specialized membrane microdomains that serve as platforms to organize signal transduction pathways [9].
• The levels of caveolin-1alpha and consequently tyrosine-14-caveolin-1 phosphorylation, but not that of caveolin-3, decreased (50%) in hypothyroid 14-day-old rats [10].
• Modulation of the caveolin-3 and Akt status in caveolae by insulin resistance in H9c2 cardiomyoblasts [11].
• Inhibitors of calcineurin and Ca2+calmodulin-dependent kinase II attenuated the phenylephrine-induced up-regulation of caveolin-3 [2].

Anatomical context of Cav3

• Immunofluorescence of adult heart revealed a distribution of Cav-3 identical to that in isolated adult cardiac myocytes [8].
• Immunofluorescence microscopy showed co-localization of Cav-3 with AC5/6, Galpha(s), beta2-AR, and mu-opioid receptors in both sarcolemmal and intracellular membranes, whereas M2-mAChR were detected only intracellularly [8].
• Caveolin-3 was expressed constitutively in some astrocytes, but not in endothelial cells; its immunoreactivity was increased in reactive astrocytes in EAE lesions [12].
• This study shows that caveolin-2 and caveolin-3 are detected at low levels in ventricular myocardium and increase dramatically with age or when neonatal cardiomyocytes are placed in culture [9].
• Caveolin-1 exists in two isoforms: the beta-isoform derivates from an alternative translational start site that creates a protein truncated by 31 amino acids, mainly expressed in endothelial cells, whereas caveolin-3 is present in muscle cells [10].

Associations of Cav3 with chemical compounds

• A redistribution of caveolin-3 and a reduction in caveolin-1 and cholesterol levels in the light fractions occurred after 10 min of reperfusion [13].
• Moreover, the [3H]QNB binding could be quantitatively immunoprecipitated from the light membrane fractions with a caveolin-3 antibody (but not a control IgG1 antibody), confirming that the m2 mAchR is targeted to caveolae after carbachol treatment [14].
• Estrogen modulation of eNOS activity and its association with caveolin-3 and calmodulin in rat hearts [15].
• Taken together, our data indicate that the decrease of glucose uptake into the cells is related to their reduced levels of caveolin-3, Akt and phosphorylated Akt in caveolae [11].
• Moreover, ionomycin increased the number of caveolae and up-regulated caveolin-3 as much as phenylephrine [2].

Physical interactions of Cav3

• Although caveolin-2 might be expected to interact in an fashion analogous to that of caveolin-3, it generally has not been detected in cardiomyocytes [9].

Co-localisations of Cav3

• Furthermore, caveolin-3 was colocalized with caveolin-1 in the same caveolae in the apical, lateral, and basal plasma membranes [16].

Other interactions of Cav3

• Immunohistochemistry demonstrated that caveolin-1 and -2 were expressed constitutively in the vascular endothelial cells and ependymal cells of the normal rat spinal cord, whereas caveolin-3 was almost exclusively localized in astrocytes [12].
• Caveolae-associated proteins in cardiomyocytes: caveolin-2 expression and interactions with caveolin-3 [9].
• RESULTS: Caveolin-3, the alpha1-adrenergic receptor, Gq and PLC-beta subtypes (PLC-beta1, -beta3) were found exclusively in the caveolar fraction in the above tissues [1].
• The lack of detectable colocalization of caveolin-3 with proteins within the endothelin post-receptor signaling system in intact myocytes argues against the presence of a preformed, caveolae-associated signalosome [17].
• In this report, using a detergent-free method for isolation of sarcolemmal caveolae from primary cultures of adult rat ventricular myocytes, we demonstrated that the muscarinic cholinergic agonist carbachol promotes the translocation of mAchR into low density gradient fractions containing most myocyte caveolin-3 and eNOS [14].

Analytical, diagnostic and therapeutic context of Cav3

• Upon immunoelectron microscopy, Cav-3 co-localized with AC5/6 and Galpha(s) in sarcolemmal and intracellular vesicles, the latter closely allied with T-tubules [8].
• Immunogold electron microscopy of tissue cryosections revealed caveolin-3, -1, and -2 to be present in caveolae in the apical, lateral, and basal plasma membranes and some vesicular profiles in the cytoplasm of sinus endothelial cells [16].
• Tissues from the bladder and urethra were collected for electron microscopy, western blotting and immunostaining for caveolin-1 and caveolin-3 [18].
• Other studies show co-immunoprecipitation of cardiomyocytes adenylyl cyclase V/VI and caveolin-3, suggesting their in vivo association [19].
• The return of caveolin-3 protein in these cells was accompanied by a fourfold increase in cav-3 mRNA, as detected by quantitative PCR, suggesting that the loss of protein in untreated cells was due to transcriptional rather than translational inhibition [20].

References