QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online January 31, 2006
Journal of Experimental Biology 209, 577-589 (2006)
Published by The Company of Biologists 2006
doi: 10.1242/jeb.02014

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Beyenbach, K. W. Articles by Wieczorek, H. Search for Related Content PubMed PubMed Citation Articles by Beyenbach, K. W. Articles by Wieczorek, H.

Review Article

The V-type H⁺ ATPase: molecular structure and function, physiological roles and regulation

Klaus W. Beyenbach^1,* and Helmut Wieczorek²

¹ Department of Biomedical Sciences, VRT 8004, Cornell University, Ithaca, NY 14853, USA
² Department of Biology/Chemistry, University of Osnabrück, 49069 Osnabrück, Germany

^* Author for correspondence (e-mail: KWB1{at}CORNELL.EDU)

Accepted 24 November 2005

It was nearly 30 years before the V-type H⁺ ATPase was admitted to the small circle of bona fide transport ATPases alongside F-type and P-type ATPases. The V-type H⁺ ATPase is an ATP-driven enzyme that transforms the energy of ATP hydrolysis to electrochemical potential differences of protons across diverse biological membranes via the primary active transport of H⁺. In turn, the transmembrane electrochemical potential of H⁺ is used to drive a variety of (i) secondary active transport systems via H⁺-dependent symporters and antiporters and (ii) channel-mediated transport systems. For example, expression of Cl^- channels or transporters next to the V-type H⁺ ATPase in vacuoles of plants and fungi and in lysosomes of animals brings about the acidification of the endosomal compartment, and the expression of the H⁺/neurotransmitter antiporter next to the V-type H⁺ ATPase concentrates neurotransmitters in synaptic vesicles.

First found in association with endosomal membranes, the V-type H⁺ ATPase is now also found in increasing examples of plasma membranes where the proton pump energizes transport across cell membranes and entire epithelia. The molecular details reveal up to 14 protein subunits arranged in (i) a cytoplasmic V₁ complex, which mediates the hydrolysis of ATP, and (ii) a membrane-embedded V₀ complex, which translocates H⁺ across the membrane. Clever experiments have revealed the V-type H⁺ ATPase as a molecular motor akin to F-type ATPases. The hydrolysis of ATP turns a rotor consisting largely of one copy of subunits D and F of the V₁ complex and a ring of six or more copies of subunit c of the V₀ complex. The rotation of the ring is thought to deliver H⁺ from the cytoplasmic to the endosomal or extracellular side of the membrane, probably via channels formed by subunit a. The reversible dissociation of V₁ and V₀ complexes is one mechanism of physiological regulation that appears to be widely conserved from yeast to animal cells. Other mechanisms, such as subunit-subunit interactions or interactions of the V-type H⁺ ATPase with other proteins that serve physiological regulation, remain to be explored. Some diseases can now be attributed to genetic alterations of specific subunits of the V-type H⁺ ATPase.

Key words: proton pump, molecular motor, V₀ complex, V₁ complex, subunit, endosomal membrane, plasma membrane, primary active transport, secondary active transport, channel-mediated transport, epithelial transport, actin, pathophysiology, genetic mutation

This article has been cited by other articles:

				J. Qi and M. Forgac Function and Subunit Interactions of the N-terminal Domain of Subunit a (Vph1p) of the Yeast V-ATPase J. Biol. Chem., July 11, 2008; 283(28): 19274 - 19282. [Abstract] [Full Text] [PDF]

				K. C. Jefferies and M. Forgac Subunit H of the Vacuolar (H+) ATPase Inhibits ATP Hydrolysis by the Free V1 Domain by Interaction with the Rotary Subunit F J. Biol. Chem., February 22, 2008; 283(8): 4512 - 4519. [Abstract] [Full Text] [PDF]

				P. M. Mangahas, X. Yu, K. G. Miller, and Z. Zhou The small GTPase Rab2 functions in the removal of apoptotic cells in Caenorhabditis elegans J. Cell Biol., January 28, 2008; 180(2): 357 - 373. [Abstract] [Full Text] [PDF]

				J. Rein, M. Voss, W. Blenau, B. Walz, and O. Baumann Hormone-induced assembly and activation of V-ATPase in blowfly salivary glands is mediated by protein kinase A Am J Physiol Cell Physiol, January 1, 2008; 294(1): C56 - C65. [Abstract] [Full Text] [PDF]

				T. G. Paunescu, L. M. Russo, N. Da Silva, J. Kovacikova, N. Mohebbi, A. N. Van Hoek, M. McKee, C. A. Wagner, S. Breton, and D. Brown Compensatory membrane expression of the V-ATPase B2 subunit isoform in renal medullary intercalated cells of B1-deficient mice Am J Physiol Renal Physiol, December 1, 2007; 293(6): F1915 - F1926. [Abstract] [Full Text] [PDF]

				A. Marmagne, M. Ferro, T. Meinnel, C. Bruley, L. Kuhn, J. Garin, H. Barbier-Brygoo, and G. Ephritikhine A High Content in Lipid-modified Peripheral Proteins and Integral Receptor Kinases Features in the Arabidopsis Plasma Membrane Proteome Mol. Cell. Proteomics, November 1, 2007; 6(11): 1980 - 1996. [Abstract] [Full Text] [PDF]

				G. Broehan, L. Zimoch, A. Wessels, B. Ertas, and H. Merzendorfer A chymotrypsin-like serine protease interacts with the chitin synthase from the midgut of the tobacco hornworm J. Exp. Biol., October 15, 2007; 210(20): 3636 - 3643. [Abstract] [Full Text] [PDF]

				X. Huang, A. Masselli, S. M. Frisch, I. C. Hunton, Y. Jiang, and J. Y. J. Wang Blockade of Tumor Necrosis Factor-induced Bid Cleavage by Caspase-resistant Rb J. Biol. Chem., October 5, 2007; 282(40): 29401 - 29413. [Abstract] [Full Text] [PDF]

				K. H. Ahmed and B. Pelster Interdependence of Ca2+ and proton movements in trout hepatocytes J. Exp. Biol., October 1, 2007; 210(19): 3473 - 3483. [Abstract] [Full Text] [PDF]

				K. K. Huynh and S. Grinstein Regulation of Vacuolar pH and Its Modulation by Some Microbial Species Microbiol. Mol. Biol. Rev., September 1, 2007; 71(3): 452 - 462. [Abstract] [Full Text] [PDF]

				J. Yang, H. Chen, I. R. Vlahov, J.-X. Cheng, and P. S. Low Characterization of the pH of Folate Receptor-Containing Endosomes and the Rate of Hydrolysis of Internalized Acid-Labile Folate-Drug Conjugates J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 462 - 468. [Abstract] [Full Text] [PDF]

				C. Hille and B. Walz A vacuolar-type H+-ATPase and a Na+/H+ exchanger contribute to intracellular pH regulation in cockroach salivary ducts J. Exp. Biol., April 15, 2007; 210(8): 1463 - 1471. [Abstract] [Full Text] [PDF]

				K. Kiselyov, A. Soyombo, and S. Muallem TRPpathies J. Physiol., February 1, 2007; 578(3): 641 - 653. [Abstract] [Full Text] [PDF]

				S. Breton and D. Brown New insights into the regulation of V-ATPase-dependent proton secretion Am J Physiol Renal Physiol, January 1, 2007; 292(1): F1 - F10. [Abstract] [Full Text] [PDF]

				B. J. Bowman, M. E. McCall, R. Baertsch, and E. J. Bowman A Model for the Proteolipid Ring and Bafilomycin/Concanamycin-binding Site in the Vacuolar ATPase of Neurospora crassa J. Biol. Chem., October 20, 2006; 281(42): 31885 - 31893. [Abstract] [Full Text] [PDF]