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Proc Natl Acad Sci U S A. Jul 15, 1992; 89(14): 6257–6261.
PMCID: PMC49479

Sensitivity to vanadate and isoforms of subunits A and B distinguish the osteoclast proton pump from other vacuolar H+ ATPases.

Abstract

Analysis of proton (H+) transport by inside-out vesicles derived from highly purified chicken osteoclast (OC) membranes has revealed the presence of a newly discovered type of vacuolar H+ ATPase (V-ATPase). Unlike vesicles derived from any other cell type or organelle, H+ transport in OC-derived vesicles is sensitive to V-ATPase inhibitors (N-ethylmaleimide and Bafilomycin A1) and vanadate (IC50, 100 microM), an inhibitor previously found to affect only P-type ATPases. The OC H+ ATPase contains several V-like subunits (115, 39, and 16 kDa) but subunits A and B of the catalytic domain of the enzyme differ from that of other V-ATPases. In OCs, subunit A has a mass of 63 kDa instead of the 67-70 kDa expressed in monocytes, macrophages, and kidney microsomes, which contain a vanadate-insensitive H+ ATPase. Moreover, two types of 57- to 60-kDa B subunits are also found: one is expressed predominantly in OCs and the other is expressed in kidney microsomes. The OC H+ pump may therefore constitute a class of H+ ATPase with a unique pharmacology and specific isoforms of two subunits in the catalytic portion of the enzyme. This H+ ATPase is involved in resorption of bone and may be expressed in a cell-specific manner, thereby opening possibilities for therapeutic intervention.

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  • Mellman I, Fuchs R, Helenius A. Acidification of the endocytic and exocytic pathways. Annu Rev Biochem. 1986;55:663–700. [PubMed]
  • Forgac M. Structure and function of vacuolar class of ATP-driven proton pumps. Physiol Rev. 1989 Jul;69(3):765–796. [PubMed]
  • Hell JW, Maycox PR, Stadler H, Jahn R. Uptake of GABA by rat brain synaptic vesicles isolated by a new procedure. EMBO J. 1988 Oct;7(10):3023–3029. [PMC free article] [PubMed]
  • Maycox PR, Deckwerth T, Hell JW, Jahn R. Glutamate uptake by brain synaptic vesicles. Energy dependence of transport and functional reconstitution in proteoliposomes. J Biol Chem. 1988 Oct 25;263(30):15423–15428. [PubMed]
  • Al-Awqati Q. Proton-translocating ATPases. Annu Rev Cell Biol. 1986;2:179–199. [PubMed]
  • Baron R, Neff L, Louvard D, Courtoy PJ. Cell-mediated extracellular acidification and bone resorption: evidence for a low pH in resorbing lacunae and localization of a 100-kD lysosomal membrane protein at the osteoclast ruffled border. J Cell Biol. 1985 Dec;101(6):2210–2222. [PMC free article] [PubMed]
  • Blair HC, Teitelbaum SL, Ghiselli R, Gluck S. Osteoclastic bone resorption by a polarized vacuolar proton pump. Science. 1989 Aug 25;245(4920):855–857. [PubMed]
  • Nelson N, Taiz L. The evolution of H+-ATPases. Trends Biochem Sci. 1989 Mar;14(3):113–116. [PubMed]
  • Bowman EJ, Siebers A, Altendorf K. Bafilomycins: a class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7972–7976. [PMC free article] [PubMed]
  • Bekker PJ, Gay CV. Biochemical characterization of an electrogenic vacuolar proton pump in purified chicken osteoclast plasma membrane vesicles. J Bone Miner Res. 1990 Jun;5(6):569–579. [PubMed]
  • Vänänen HK, Karhukorpi EK, Sundquist K, Wallmark B, Roininen I, Hentunen T, Tuukkanen J, Lakkakorpi P. Evidence for the presence of a proton pump of the vacuolar H(+)-ATPase type in the ruffled borders of osteoclasts. J Cell Biol. 1990 Sep;111(3):1305–1311. [PMC free article] [PubMed]
  • Nelson N. Structure and pharmacology of the proton-ATPases. Trends Pharmacol Sci. 1991 Feb;12(2):71–75. [PubMed]
  • Wang ZQ, Gluck S. Isolation and properties of bovine kidney brush border vacuolar H(+)-ATPase. A proton pump with enzymatic and structural differences from kidney microsomal H(+)-ATPase. J Biol Chem. 1990 Dec 15;265(35):21957–21965. [PubMed]
  • Zambonin Zallone A, Teti A, Primavera MV. Isolated osteoclasts in primary culture: first observations on structure and survival in culture media. Anat Embryol (Berl) 1982 Dec;165(3):405–413. [PubMed]
  • Achee FM, Togulga G, Gabay S. Studies of monoamine oxidases: properties of the enzyme in bovine and rabbit brain mitochondria. J Neurochem. 1974 May;22(5):651–661. [PubMed]
  • Fuchs R, Mâle P, Mellman I. Acidification and ion permeabilities of highly purified rat liver endosomes. J Biol Chem. 1989 Feb 5;264(4):2212–2220. [PubMed]
  • Lauter CJ, Solyom A, Trams EG. Comparative studies on enzyme markers of liver plasma membranes. Biochim Biophys Acta. 1972 May 9;266(2):511–523. [PubMed]
  • Varshney GC, Henry J, Kahn A, Phan-Dinh-Tuy F. Tyrosine kinases in normal human blood cells. Platelet but not erythrocyte band 3 tyrosine kinase is p60c-src. FEBS Lett. 1986 Sep 1;205(1):97–103. [PubMed]
  • Wang SY, Moriyama Y, Mandel M, Hulmes JD, Pan YC, Danho W, Nelson H, Nelson N. Cloning of cDNA encoding a 32-kDa protein. An accessory polypeptide of the H+-ATPase from chromaffin granules. J Biol Chem. 1988 Nov 25;263(33):17638–17642. [PubMed]
  • Lai SP, Randall SK, Sze H. Peripheral and integral subunits of the tonoplast H+-ATPase from oat roots. J Biol Chem. 1988 Nov 15;263(32):16731–16737. [PubMed]
  • Bowman EJ, Tenney K, Bowman BJ. Isolation of genes encoding the Neurospora vacuolar ATPase. Analysis of vma-1 encoding the 67-kDa subunit reveals homology to other ATPases. J Biol Chem. 1988 Oct 5;263(28):13994–14001. [PubMed]
  • Südhof TC, Fried VA, Stone DK, Johnston PA, Xie XS. Human endomembrane H+ pump strongly resembles the ATP-synthetase of Archaebacteria. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6067–6071. [PMC free article] [PubMed]
  • Billecocq A, Emanuel JR, Levenson R, Baron R. 1 alpha,25-dihydroxyvitamin D3 regulates the expression of carbonic anhydrase II in nonerythroid avian bone marrow cells. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6470–6474. [PMC free article] [PubMed]
  • Gluck S, Caldwell J. Immunoaffinity purification and characterization of vacuolar H+ATPase from bovine kidney. J Biol Chem. 1987 Nov 15;262(32):15780–15789. [PubMed]
  • Schmid S, Fuchs R, Kielian M, Helenius A, Mellman I. Acidification of endosome subpopulations in wild-type Chinese hamster ovary cells and temperature-sensitive acidification-defective mutants. J Cell Biol. 1989 Apr;108(4):1291–1300. [PMC free article] [PubMed]
  • Glazer AN. Light guides. Directional energy transfer in a photosynthetic antenna. J Biol Chem. 1989 Jan 5;264(1):1–4. [PubMed]
  • Brown D, Gluck S, Hartwig J. Structure of the novel membrane-coating material in proton-secreting epithelial cells and identification as an H+ATPase. J Cell Biol. 1987 Oct;105(4):1637–1648. [PMC free article] [PubMed]
  • Moriyama Y, Nelson N. Purification and properties of a vanadate- and N-ethylmaleimide-sensitive ATPase from chromaffin granule membranes. J Biol Chem. 1988 Jun 15;263(17):8521–8527. [PubMed]
  • Bowman BJ, Allen R, Wechser MA, Bowman EJ. Isolation of genes encoding the Neurospora vacuolar ATPase. Analysis of vma-2 encoding the 57-kDa polypeptide and comparison to vma-1. J Biol Chem. 1988 Oct 5;263(28):14002–14007. [PubMed]
  • Mandala SM, Slayman CW. The amino and carboxyl termini of the Neurospora plasma membrane H+-ATPase are cytoplasmically located. J Biol Chem. 1989 Sep 25;264(27):16276–16281. [PubMed]
  • Fuchs R, Schmid S, Mellman I. A possible role for Na+,K+-ATPase in regulating ATP-dependent endosome acidification. Proc Natl Acad Sci U S A. 1989 Jan;86(2):539–543. [PMC free article] [PubMed]
  • Yamashiro DJ, Fluss SR, Maxfield FR. Acidification of endocytic vesicles by an ATP-dependent proton pump. J Cell Biol. 1983 Sep;97(3):929–934. [PMC free article] [PubMed]
  • Ohkuma S, Moriyama Y, Takano T. Identification and characterization of a proton pump on lysosomes by fluorescein-isothiocyanate-dextran fluorescence. Proc Natl Acad Sci U S A. 1982 May;79(9):2758–2762. [PMC free article] [PubMed]
  • Ysern X, Amzel LM, Pedersen PL. ATP synthases--structure of the F1-moiety and its relationship to function and mechanism. J Bioenerg Biomembr. 1988 Aug;20(4):423–450. [PubMed]
  • Futai M, Noumi T, Maeda M. Mechanism of F1-ATPase studied by the genetic approach. J Bioenerg Biomembr. 1988 Aug;20(4):469–480. [PubMed]
  • Bowman BJ, Dschida WJ, Harris T, Bowman EJ. The vacuolar ATPase of Neurospora crassa contains an F1-like structure. J Biol Chem. 1989 Sep 15;264(26):15606–15612. [PubMed]

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