• We show that XMEA is caused by hypomorphic alleles of the VMA21 gene, that VMA21 is the diverged human ortholog of the yeast Vma21p protein, and that like Vma21p, VMA21 is an essential assembly chaperone of the vacuolar ATPase (V-ATPase), the principal mammalian proton pump complex. (nih.gov)
  • V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. (wikipedia.org)
  • 1990. Molecular analysis of the yeast VPS3 gene and the role of its product in vacuolar protein sorting and vacuolar segregation during the cell cycle. . (ucsb.edu)
  • 1989. Characterization of genes required for protein sorting and vacuolar function in the yeast Saccharomyces cerevisiae. . (ucsb.edu)
  • 1989. Protein sorting in yeast: the role of the vacuolar proton-translocating ATPase. . (ucsb.edu)
  • 1987. Protein sorting in yeast: the localization determinant of yeast vacuolar carboxypeptidase Y resides in the propeptide. . (ucsb.edu)
  • 1986. Overproduction-induced mislocalization of a yeast vacuolar protein allows isolation of its structural gene. . (ucsb.edu)
  • 1986. Protein sorting in yeast: mutants defective in vacuole biogenesis mislocalize vacuolar proteins into the late secretory pathway. . (ucsb.edu)
  • The V-ATPase complex regulates non-canonical Atg8-family protein lipidation through ATG16L1 recruitment. (babraham.ac.uk)
  • Unlike reversible disassembly, which requires ATP hydrolysis on V 1 to break protein-protein interactions, Oxr1p mediated disassembly of V-ATPase is ATP independent and therefore a novel mode of activity regulation. (upstate.edu)
  • ATPase H+ Transporting Accessory Protein 2 is associated with adenosine triphosphatases (ATPases). (creative-biolabs.com)
  • The encoded protein has been found associated with the transmembrane sector of the V-type ATPases. (creative-biolabs.com)
  • To examine interactions between G proteins and the H + -ATPase, we performed immunocytochemical studies on perfusion-fixed sections of rat kidney using polyclonal anti-G protein antibodies and E11, a mouse monoclonal antibody to the 31-kDa subunit of the vacuolar H + -ATPase. (wustl.edu)
  • Some intercalated cells that stained prominently for the proton pump in the apical membrane did not, however, stain for any G protein α-subunit. (wustl.edu)
  • It has a membrane peripheral V1 sector for ATP hydrolysis and an integral V0 for proton translocation. (lu.se)
  • URA3 null mutants are not able to grow on a medium buffered at pH 7.5, they fail to accumulate quinacrine into their vacuoles and the other subunits of the catalytic sector are not assembled onto the vacuolar membrane in its absence. (tau.ac.il)
  • In fungi, two recognized mechanisms contribute to pH homeostasis: the plasma membrane proton-pumping ATPase that exports excess protons and the vacuolar proton-pumping ATPase (V-ATPase) that mediates vacuolar proton uptake. (oregonstate.edu)
  • By confocal microscopy, PEP3-overexpressing cells stained with the vacuolar membrane-specific dye, FM4-64 had more fragmented vacuoles than the wild-type control. (oregonstate.edu)
  • V-ATPase is made of two subcomplexes: a cytosolic V 1 that carries out ATP hydrolysis, and a membrane bound V o that is responsible for proton translocation. (upstate.edu)
  • Journal cover: V-ATPase is regulated by disassembly into soluble V 1 (shown in cyan) and membrane integral V o (shown in gold) subcomplexes. (upstate.edu)
  • All such systems are multisubunit complexes with at least 3 dissimilar subunits embedded as a complex in the membrane (F 0 , a:b:c = 1:2:~12) and (usually) at least 5 dissimilar subunits attached to F 0 (F 1 , α:β:γ:δ:ε = 3:3:1:1:1 for F-type ATPases). (tcdb.org)
  • They are coupled to the transport of protons across a membrane. (nih.gov)
  • We propose that one function of the H+-PPiase may be to act as an ancillary enzyme that maintains the proton-motive force across the vacuolar membrane when the activity of the tonoplast H+-ATPase is restricted by substrate availability. (ox.ac.uk)
  • We prepared medullary membrane vesicles highly enriched for the H + -ATPase to examine possible functional interactions of G proteins with the H + -ATPase by the acridine orange method. (wustl.edu)
  • The proton flow responsible for decreased pH values inside mitochondrial cristae and membrane invaginations of cyanobacteria has been c. (shengsci.com)
  • Here, we report that overexpression of PEP3 which encodes a component of the HOPS and CORVET complexes involved in vacuolar biogenesis, shortened lag phase in Saccharomyces cerevisiae exposed to acetic acid stress. (oregonstate.edu)
  • While individual V 1 and V o subcomplexes are locked in specific rotary states, the in vitro assembled complexes populated three rotary states, similar to what was previously observed for native V-ATPase. (upstate.edu)
  • Once confirmed by dose-response assays (EC(50)=26 microM), we verified V-ATPase inhibition by disulfiram in secondary assays that measured ATP hydrolysis in vacuolar membranes. (unm.edu)
  • The rotor (which consists of the c, ε and γ subunits) is believed to rotate relative to the stator in response to either ATP hydrolysis by F 1 or proton transport through F 0 . (tcdb.org)
  • To clarify the kinetic characteristics and ionic requirements of the tonoplast H+-translocating inorganic pyrophosphatase (H+-PPiase), PPi hydrolysis and PPi-dependent H+ transport were studied in tonoplast vesicles isolated from leaf mesophyll tissue of Kalanchoë daigremontiana Hamet et Perrier de la Bâthie. (ox.ac.uk)
  • The model also helped distinguish differences in malate concentration among the three cultivars and between the pre and post-harvest stages by highlighting the probable importance of proton pump activity and particularly of the free energy of ATP hydrolysis and vacuolar pH. (biomedcentral.com)
  • We have shown that this process is triggered by recruitment of ATG16L1 by the vacuolar-type H-translocating ATPase (V-ATPase) proton pump, suggesting a role for pH sensing in recruitment of Atg8-family proteins to single membranes. (babraham.ac.uk)
  • Vacuolar-type ATPase: A proton pump to lysosomal trafficking. (doshisha.ac.jp)
  • The CV-system is also assumed to be involved in Ca 2+ -transport since it contains a PMCA-type Ca 2+ -ATPase (PAT1), calmodulin [ 3 ] and a vacuolar proton pump that establishes a proton gradient for Ca 2+ -transport [ 4 ]. (biomedcentral.com)
  • The vacuolar ATPase (V-ATPase) is a highly conserved rotary motor proton pump that plays an essential role in cellular housekeeping functions. (upstate.edu)
  • All eukaryotic F-type ATPases pump 3-4 H + out of mitochondria, or into thylakoids of chloroplasts, per ATP hydrolyzed. (tcdb.org)
  • Bacterial F-type ATPases pump 3-4 H + and/or Na + (depending on the system) out of the cell per ATP hydrolyzed. (tcdb.org)
  • V-type ATPases may pump 2-3 H + per ATP hydrolyzed, and these enzymes cannot catalyze pmf-driven ATP synthesis. (tcdb.org)
  • Yeast vacuoles contain an H + -ATPase that acidifies the vacuolar lumen and generates an electrochemical gradient of protons across their membranes. (tau.ac.il)
  • abstract = "Yeast vacuoles contain an H+-ATPase that acidifies the vacuolar lumen and generates an electrochemical gradient of protons across their membranes. (tau.ac.il)
  • This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. (wikipedia.org)
  • Hence, the multisubunit enzyme vacuolar ATPase (V-ATPase), which is mainly responsible for endosome acidification in the cell, represents an attractive target for antiviral strategies. (lih.lu)
  • A specific inhibitor of vacuolar ATPase, concanamycin A, interrupted both the acidification and degradation in phagosomes in both species, suggesting the ubiquitous role of vacuolar ATPase in the acidification and degradation in Entamoeba. (elsevierpure.com)
  • 1989. Acidification of the lysosome-like vacuole and the vacuolar H+-ATPase are deficient in two yeast mutants that fail to sort vacuolar proteins. . (ucsb.edu)
  • Proton-translocating ATPases have fundamental roles in energy conservation, secondary active transport, acidification of intracellular compartments, and cellular pH homeostasis. (creative-biolabs.com)
  • Electron cryoEM structures of mitochondrial, chloroplast, and bacterial ATP synthases have revealed the architecture of the FO region, helping to explain the mechanisms of proton translocation, dimerization of the enzyme in mitochondria, and cristae formation. (tcdb.org)
  • The unique bifurcated oxidation of ubiquinol at center P (Qo) of the cytochrome bc1 complex is the reaction within the Q-cycle reaction scheme that is most critical for the link between electron transfer and vectorial proton translocation. (shengsci.com)
  • Identification of inhibitors of vacuolar proton-translocating ATPase pumps in yeast by high-throughput screening flow cytometry. (unm.edu)
  • We used yeast cells loaded with BCECF to screen a small chemical library of structurally diverse compounds to identify V-ATPase inhibitors. (unm.edu)
  • The infection inhibitory potencies of saliphenylhalamide, a proven V-ATPase inhibitor, and its derivatives, as well as those of other V-ATPase inhibitors, were analyzed on different HPV types in relevant cell lines. (lih.lu)
  • Variation in the selectivity indices among V-ATPase inhibitors was high, while variation for the same inhibitor against different HPV subtypes was low, indicating that broad-spectrum anti-HPV activity can be provided. (lih.lu)
  • Here, using pharmacological inhibitors, we investigate a role for V-ATPase during non-canonical autophagy. (babraham.ac.uk)
  • V-type proton ATPase subunit e 1 is an enzyme that in humans is encoded by the ATP6V0E1 gene. (wikipedia.org)
  • The V-ATPase is an heteromultimeric enzyme composed of at least thirteen different subunits. (lu.se)
  • 1986. PEP4 gene of Saccharomyces cerevisiae encodes proteinase A, a vacuolar enzyme required for processing of vacuolar precursors. . (ucsb.edu)
  • We measured fluorescence intensity of BCECF trapped in yeast vacuoles, acidic compartments equivalent to lysosomes where vacuolar proton-translocating ATPases (V-ATPases) are abundant. (unm.edu)
  • Epitope-tagged Vma7p was constructed and the proton uptake activity of isolated vacuoles from this yeast strain was markedly inhibited by a monoclonal antibody against the epitope-tag. (tau.ac.il)
  • V-type ATPases are found in vacuoles of eukaryotes and in bacteria. (tcdb.org)
  • Gene dosage-dependent secretion of yeast vacuolar carboxypeptidase Y. . J Cell Biol. (ucsb.edu)
  • Because V-ATPases maintain a low pH in the vacuolar lumen, V-ATPase inhibition by concanamycin A alkalinized the vacuole and increased BCECF fluorescence. (unm.edu)
  • The vast majority of proteins entering the secretory pathway are synthesized on ribosomes docked at ER translocons and are co-transationally translocated into the ER lumen. (stanford.edu)
  • The crystal structure of the S. cerevisiae c-subunit ring with bound oligomycin revealed the inhibitor docked on the outer face of the proton-binding sites, deep in the transmembrane region ( Zhou and Faraldo-Gómez 2018 ). (tcdb.org)
  • Acidic means that the stores are equipped with a V-type H + -ATPase. (biomedcentral.com)
  • V-ATPase a3 isoform mutations identified in osteopetrosis patients abolish its expression and disrupt osteoclast function. (doshisha.ac.jp)
  • Isoform-specific gene disruptions reveal a role for the V-ATPase subunit a4 isoform in the invasiveness of 4T1-12B breast cancer cells. (doshisha.ac.jp)
  • Extracellular Adenosine Stimulates Vacuolar ATPase-Dependent Proton Secretion in Medullary Intercalated Cells. (harvard.edu)
  • Thus, we detected an increase of fluorescence intensity after short- and long-term inhibition of V-ATPase function. (unm.edu)
  • In the present study, we show that V-ATPase is required for human papillomavirus (HPV) infection and that uncoating/disassembly but not endocytosis is affected by V-ATPase inhibition. (lih.lu)
  • V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. (wikipedia.org)
  • Although a vacuolar role in maintaining proper cytosolic pH has been proposed, the necessity for a functional vacuole is not completely understood [13] , and has probably a multifactorial nature that will be discussed further in other sections of this review. (microbialcell.com)
  • Therefore, one can hypothesize that malate accumulation in fruit cells is mainly controlled at the level of vacuolar storage, and that metabolism responds appropriately to regulate the cytosolic concentration of malate since it plays a fundamental role in the regulation of cytosolic pH [ 14 ]. (biomedcentral.com)
  • The decomposition of the organic matter, the imbalance of the N, S, and C cycles, the excess in the cation uptake on anions and the N fixation by the legumes influence the concentration of protons [H + ] in the soil solution. (frontiersin.org)
  • This model is based on a simplified representation of the functioning of the tonoplast to simulate vacuolar malate storage and thus appears to be a good framework to study malate accumulation in fleshy fruit. (biomedcentral.com)
  • When a 14-kDa polypeptide was suggested to be a subunit of a specialized V-ATPase in Manduca sexta, and a homologous short sequence was detected downstream of the UGA1 gene in yeast, we cloned this counterpart gene from yeast. (tau.ac.il)
  • The inhibitory action of disulfiram against V-ATPase pumps revealed a novel effect previously unknown for this compound. (unm.edu)
  • A cold inactivation experiment demonstrated that Vma7p is a genuine subunit of the catalytic sector of V-ATPase and it is denoted as subunit F. (tau.ac.il)
  • There are three classes of ATPases-F, P, and V. The vacuolar (V-type) ATPases have a transmembrane proton-conducting sector and an extramembrane catalytic sector. (creative-biolabs.com)
  • F-type ATPases are found in eukaryotic mitochondria and chloroplasts as well as in bacteria. (tcdb.org)
  • A recent study from the Wilkens lab in collaboration with Seoul National University uncovered a novel mechanism of yeast V-ATPase regulation based on biochemical experiments and cryo electron microscopy (cryo-EM) structures of holo V-ATPase and Oxr1 bound V 1 subcomplex. (upstate.edu)
  • However, the regulation of vacuolar malate storage throughout fruit development, and the origins of the phenotypic variability of the malate concentration within fruit species remain to be clarified. (biomedcentral.com)
  • The enzyme's proton pumping function is regulated by a unique process called "reversible disassembly", wherein V 1 dissociates from V o in a for example nutrient dependent manner. (upstate.edu)
  • Biochemical experiments showed that Oxr1p binds and promotes V-ATPase disassembly. (upstate.edu)
  • The F 1 portion of the bovine mitochondrial F-type ATPase has been solved to 2.8 Å resolution. (tcdb.org)
  • According to the model, vacuolar composition, in particular potassium and organic acid concentrations, had an important effect on malate accumulation. (biomedcentral.com)
  • Possible roles for a mutated proton channel in the pathogenesis of cystic disease were considered. (johnshopkins.edu)
  • Further experiments will be required to uncover the physiological role of the interaction suof Oxr1 with the V-ATPase, and whether the observations obtained for the yeast system are conserved in higher organisms, including humans. (upstate.edu)
  • Based on an indirect growth assay, the PEP3-overexpression strain exhibited higher V-ATPase activity. (oregonstate.edu)
  • Not surprisingly, V-ATPase activity (or loss thereof) has been linked to several disease states including renal tubular acidosis, osteoporosis, neurodegeneration, and cancer. (upstate.edu)
  • Likewise, V-ATPase-deficient mutant cells had greater fluorescence intensity than wild-type cells. (unm.edu)
  • Several studies suggest that malate accumulation in fruit cells is controlled at the level of vacuolar storage. (biomedcentral.com)
  • Intercalated cells expressing the H + -ATPase are also prevalent in this nephron segment. (wustl.edu)
  • Gα s subunits were consistently not associated with cells containing the H + -ATPase in this nephron segment, whereas Gα i-2 , Gα 1-3 , and Gα q/11 were. (wustl.edu)
  • Gαs subunits were consistently not associated with cells containing the H+-ATPase in this nephron segment, whereas Gαi-2, Gα1-3, and Gαq/11 were. (wustl.edu)
  • Na(+)-translocating NADH-quinone reductase of marine and halophilic bacteria. (shengsci.com)
  • By integrating these findings, we propose an updated and unifying mechanism for noncanonical autophagy, centered on ATG16L1 and V-ATPase. (babraham.ac.uk)
  • Upon V0-V1 binding, V-ATPase recruits ATG16L1, via K490, during LC3-associated phagocytosis (LAP), STING- and drug-induced CASM, indicating a common mechanism. (babraham.ac.uk)
  • While the vacuolar pH of the wild-type strain grown in the presence of 80 mM acetic acid was significantly higher than in the absence of added acid, no significant difference was observed in vacuolar pH of the overexpression strain grown either in the presence or absence of 80 mM acetic acid. (oregonstate.edu)
  • Proton transport was significantly increased in the presence of guanosine 5′-O-(3-thiotriphosphate), and this held true in the absence of chloride. (wustl.edu)