Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vacuolar-type H(+)-ATPase (V-ATPase) is a multi-subunit enzyme that has important roles in the acidification of a variety of intracellular compartments and some extracellular milieus. Four isoforms for the membrane-intrinsic subunit (subunit a) of the V-ATPase have been identified in mammals, and they confer distinct cellular localizations and activities on the proton pump. We found that V-ATPase with the a3 isoform is highly expressed in pancreatic islets, and is localized to membranes of insulin-containing secretory granules in beta-cells. oc/oc mice, which have a null mutation at the a3 locus, exhibited a reduced level of insulin in the blood, even with high glucose administration. However, islet lysates contained mature insulin, and the ratio of the amount of insulin to proinsulin in oc/oc islets was similar to that of wild-type islets, indicating that processing of insulin was normal even in the absence of the a3 function. The insulin contents of oc/oc islets were reduced slightly, but this was not significant enough to explain the reduced levels of the blood insulin. The secretion of insulin from isolated islets in response to glucose or depolarizing stimulation was impaired. These results suggest that the a3 isoform of V-ATPase has a regulatory function in the exocytosis of insulin secretion.
...
PMID:The a3 isoform of V-ATPase regulates insulin secretion from pancreatic beta-cells. 1704 93

Vacuolar-type H(+)-ATPase (V-ATPase or V-type ATPase) is a multisubunit complex comprised of a water-soluble V(1) complex, responsible for ATP hydrolysis, and a membrane-embedded V(o) complex, responsible for proton translocation. The V(1) complex of Thermus thermophilus V-ATPase has the subunit composition of A(3)B(3)DF, in which the A and B subunits form a hexameric ring structure. A central stalk composed of the D and F subunits penetrates the ring. In this study, we investigated the pathway for assembly of the V(1) complex by reconstituting the V(1) complex from the monomeric A and B subunits and DF subcomplex in vitro. Assembly of these components into the V(1) complex required binding of ATP to the A subunit, although hydrolysis of ATP is not necessary. In the absence of the DF subcomplex, the A and B monomers assembled into A(1)B(1) and A(3)B(3) subcomplexes in an ATP binding-dependent manner, suggesting that ATP binding-dependent interaction between the A and B subunits is a crucial step of assembly into V(1) complex. Kinetic analysis of assembly of the A and B monomers into the A(1)B(1) heterodimer using fluorescence resonance energy transfer indicated that the A subunit binds ATP prior to binding the B subunit. Kinetics of binding of a fluorescent ADP analog, N-methylanthraniloyl ADP (mant-ADP), to the monomeric A subunit also supported the rapid nucleotide binding to the A subunit.
...
PMID:Reconstitution in vitro of V1 complex of Thermus thermophilus V-ATPase revealed that ATP binding to the A subunit is crucial for V1 formation. 1705 May 29

The osteoclast is a specialized multinucleated variant of the macrophage family. It degrades mineralized tissue, and is required for modeling and remodeling of bone. The osteoclast has long been known to require vitamin D for its differentiation and to be regulated by parathyroid hormone via circulating Ca(2+) levels. Two local signals important in osteoclast survival and differentiation, CSF-1 and RANKL, were characterized by the mid-1990 s. A basic framework of specialized cell attachment and resorption molecules was also clear by that time, including the alpha(v)beta(3) integrin, the key adhesion molecule of the mature osteoclast, the highly expressed vacuolar-type H(+)-ATPase that drives acid secretion to dissolve mineral, and cathepsin K, the predominant acid proteinase for collagenolysis. Recently, additional detail has been added to this framework, showing that the osteoclast has more complex regulation than was previously believed. These include the findings that one component of the V-H(+)-ATPase is unique to the osteoclast, that chloride transport and probably Cl(-)/H(+) exchange are also required for mineral degradation, and that additional receptors besides RANK and Fms regulate osteoclast formation and survival. Additional receptors include estrogen receptor-alpha, TNF-family receptors other than RANK, and, at least in some cases, glycoprotein hormone receptors including the TSH-R and the FSH-R. Challenges in understanding osteoclast biology include how the signalling mechanisms function cooperatively. Recent findings suggest that there is a network of cytoplasmic adapters, including Gab-2 and BCAR1, which are modified by multiple signalling mechanisms and which serve to integrate the signalling pathways.
...
PMID:Osteoclastic differentiation and function regulated by old and new pathways. 1711 68

Cells of the dopaminergically innervated salivary ducts in the cockroach Periplaneta americana have a vacuolar-type H(+)-ATPase (V-ATPase) of unknown function in their apical membrane. We have studied whether dopamine affects intracellular pH (pH(i)) in duct cells and whether and to what extent the apical V-ATPase contributes to pH(i) regulation. pH(i) measurements with double-barrelled pH-sensitive microelectrodes and the fluorescent dye BCECF have revealed: (1) the steady-state pH(i) is 7.3+/-0.1; (2) dopamine induces a dose-dependent acidification up to pH 6.9+/-0.1 at 1 micromol l(-1) dopamine, EC(50) at 30 nmol l(-1) dopamine; (3) V-ATPase inhibition with concanamycin A or Na(+)-free physiological saline (PS) does not affect the steady-state pH(i); (4) concanamycin A, Na(+) -free PS and Na(+)/H(+) exchange inhibition with 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) each reduce the rate of pH(i) recovery from a dopamine-induced acidification or an acidification induced by an NH(4)Cl pulse; (5) pH(i) recovery after NH(4)Cl-induced acidification is almost completely blocked by concanamycin A in Na(+)-free PS or by concanamycin A applied together with EIPA; (6) pH(i) recovery after dopamine-induced acidification is also completely blocked by concanamycin A in Na(+)-free PS but only partially blocked by concanamycin A applied together with EIPA. We therefore conclude that the apical V-ATPase and a basolateral Na(+)/H(+) exchange play a minor role in steady-state pH(i) regulation but contribute both to H(+) extrusion after an acute dopamine- or NH(4)Cl-induced acid load.
...
PMID:A vacuolar-type H+-ATPase and a Na+/H+ exchanger contribute to intracellular pH regulation in cockroach salivary ducts. 1740 Nov 29

In this study, we have studied the expression, localization, and functionality of vacuolar-type H(+)-ATPase (vH(+)-ATPase) and Na(+)/K(+)-ATPase in the bovine rumen epithelium. Compared with the intracellular pH (pH(i)) of control rumen epithelial cells (REC; 7.06 +/- 0.07), application of inhibitors selective for vH(+)-ATPase (foliomycin) and Na(+)/K(+)-ATPase (ouabain) reduced pH(i) by 0.10 +/- 0.03 and 0.18 +/- 0.03 pH-units, respectively, thereby verifying the existence of both functional proteins. Results from qRT-PCR and immunoblotting clearly confirm the expression of vH(+)-ATPase B subunit in REC. However, the amount of Na(+)/K(+)-ATPase mRNA and protein is tenfold and 11-fold of those of vH(+)-ATPase subunit B, respectively, reflecting a lower overall abundance of the latter in REC. Na(+)/K(+)-ATPase immunostaining has revealed the protein in the plasma membrane of all REC from the stratum basale to stratum granulosum, with the highest abundance in basal cells. In contrast, the vH(+)-ATPase B subunit has been detected in groups of cells only, mainly localized in the stratum spinosum and stratum granulosum of the epithelium. Furthermore, vH(+)-ATPase has been detected in the cell membrane and in intracellular pools. Thus, functional vacuolar-type H(+) pumps are expressed in REC and probably play a role in the adaptation of epithelial transport processes.
...
PMID:Molecular identification, immunolocalization, and functional activity of a vacuolar-type H(+)-ATPase in bovine rumen epithelium. 1798 83

Blowfly salivary gland cells have a vacuolar-type H(+)-ATPase (V-ATPase) in their apical membrane that energizes secretion of a KCl-rich saliva upon stimulation with serotonin (5-hydroxytryptamine, 5-HT). We have used BCECF to study microfluometrically whether V-ATPase and carbonic anhydrase (CA) are involved in intracellular pH (pH(i)) regulation, and we have localized CA activity by histochemistry. We show: (1) mean pH(i) in salivary gland cells is 7.5+/-0.3 pH units (N=96), higher than that expected from passive H(+) distribution; (2) low 5-HT concentrations (0.3-3 nmol l(-1)) induce a dose-dependent acidification of up to 0.2 pH units, with 5-HT concentrations >10 nmol l(-1), causing monophasic or multiphasic pH changes; (3) the acidifying effect of 5-HT is mimicked by bath application of cAMP, forskolin or IBMX; (4) salivary gland cells exhibit CA activity; (5) CA inhibition with acetazolamide and V-ATPase inhibition with concanamycin A lead to a slow acidification of steady-state pH(i); (6) 5-HT stimuli in the presence of acetazolamide induce an alkalinization that can be decreased by simultaneous application of the V-ATPase inhibitor concanamycin A; (7) concanamycin A removes alkali-going components from multiphasic 5-HT-induced pH changes; (8) NHE activity and a Cl(-)-dependent process are involved in generating 5-HT-induced pH changes; (9) the salivary glands probably contain a Na(+)-driven amino acid transporter. We conclude that V-ATPase and CA contribute to steady-state pH(i) regulation and 5-HT-induced outward H(+) pumping does not cause an alkalinization of pH(i) because of cytosolic H(+) accumulation attributable to stimulated cellular respiration and AE activity, masking the alkalizing effect of V-ATPase-mediated acid extrusion.
...
PMID:Intracellular pH homeostasis and serotonin-induced pH changes in Calliphora salivary glands: the contribution of V-ATPase and carbonic anhydrase. 1828 44

The melanosome, an organelle specialized for melanin synthesis, is one of the lysosome-related organelles. Its lumen is reported to be acidified by vacuolar-type H(+)-ATPase (V-ATPase). Mammalian V-ATPase exhibits structural diversity in its subunit isoforms; with regard to membrane intrinsic subunit a, four isoforms (a1-a4) have been found to be localized to distinct subcellular compartments. In this study, we have shown that the a3 isoform is co-localized with a melanosome marker protein, Pmel17, in mouse melanocytes. Acidotropic probes (LysoSensor and DAMP) accumulate in non-pigmented Pmel17-positive melanosomes, and DAMP accumulation is sensitive to bafilomycin A1, a specific inhibitor of V-ATPase. However, none of the subunit a isoforms is associated with highly pigmented mature melanosomes, in which the acidotropic probes are also not accumulated. oc/oc mice, which have a null mutation at the a3 locus, show no obvious defects in melanogenesis. In the mutant melanocytes, the expression of the a2 isoform is modestly elevated, and a considerable fraction of this isoform is localized to premature melanosomes. These observations suggest that the V-ATPase keeps the lumen of premature melanosomes acidic, whereas melanosomal acidification is less significant in mature melanosomes.
...
PMID:Vacuolar-type H(+)-ATPase with the a3 isoform is the proton pump on premature melanosomes. 1840 55

To investigate the involvement of the yolk-sac membrane in ion absorption, developmental changes in whole-body cation contents, cellular localization of vacuolar-type H(+)-ATPase (V-ATPase), and size and density of pavement and chloride cells in the yolk-sac membrane were examined in tilapia (Oreochromis mossambicus) larvae in fresh water (FW) and those transferred to seawater (SW) at 2 days before hatching (day-2). The whole-body content of Na(+) in embryos and larvae adapted to both FW and SW increased constantly from day-2 to day 10, although they were not fed through the experiment. The yolk-sac membrane of FW larvae at days 0 and 2 showed V-ATPase immunoreactivity in pavement cells, but not in chloride cells. No positive immunoreactivity was detected in SW larvae. Whole-mount immunocytochemistry showed that some pavement cells were intensively immunoreactive, whereas others were less or not immunoreactive. Electron-microscopic immunocytochemistry revealed that V-ATPase immunoreactivity was present in the apical regions of pavement cells in FW larvae, especially in their ridges. The pavement cells in FW larvae were significantly smaller in size but higher in density than those in SW. These results suggest that pavement cells are the site of active Na(+) uptake in exchange for H(+) secretion through V-ATPase in FW-adapted tilapia during early life stages.
...
PMID:Immunolocalization of Vacuolar-Type H(+)-ATPase in the Yolk-Sac Membrane of Tilapia (Oreochromis mossambicus) Larvae. 1846 23

Vacuolar-type H(+)-ATPase (V-ATPase) catalyzes ATP synthesis and hydrolysis coupled with proton translocation across membranes via a rotary motor mechanism. Here we report biochemical and biophysical catalytic properties of V-ATPase from Thermus thermophilus. ATP hydrolysis of V-ATPase was severely inhibited by entrapment of Mg-ADP in the catalytic site. In contrast, the enzyme was very active for ATP synthesis (approximately 70 s(-1)) with the K(m) values for ADP and phosphate being 4.7 +/- 0.5 and 460 +/- 30 microm, respectively. Single molecule observation showed V-ATPase rotated in a 120 degrees stepwise manner, and analysis of dwelling time allowed the binding rate constant k(on) for ATP to be estimated ( approximately 1.1 x 10(6) m(-1) s(-1)), which was much lower than the k(on) (= V(max)/K(m)) for ADP ( approximately 1.4 x 10(7) m(-1) s(-1)). The slower k(on)(ATP) than k(on)(ADP) and strong Mg-ADP inhibition may contribute to prevent wasteful consumption of ATP under in vivo conditions when the proton motive force collapses.
...
PMID:ATP hydrolysis and synthesis of a rotary motor V-ATPase from Thermus thermophilus. 1849 67

The multi-subunit vacuolar-type H(+)-ATPase consists of a V(1) domain (A-H subunits) catalyzing ATP hydrolysis and a V(0) domain (a, c, c', c", d, e) responsible for H(+) translocation. The mammalian V(0) d subunit is one of the least-well characterized, and its function and position within the pump are still unclear. It has two different forms encoded by separate genes, d1 being ubiquitous while d2 is predominantly expressed at the cell surface in kidney and osteoclast. To determine whether it forms part of the pump's central stalk as suggested by bacterial A-ATPase studies, or is peripheral as hypothesized from a yeast model, we investigated both human d subunit isoforms. In silico structural modelling demonstrated that human d1 and d2 are structural orthologues of bacterial subunit C, despite poor sequence identity. Expression studies of d1 and d2 showed that each can pull down the central stalk's D and F subunits from human kidney membrane, and in vitro studies using D and F further showed that the interactions between these proteins and the d subunit is direct. These data indicate that the d subunit in man is centrally located within the pump and is thus important in its rotary mechanism.
...
PMID:The d subunit plays a central role in human vacuolar H(+)-ATPases. 1875 60


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---