HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 22, 20013-20018, May 30, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/22/20013    most recent M210077200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Su, Y. Articles by Karet, F. E. Search for Related Content PubMed PubMed Citation Articles by Su, Y. Articles by Karet, F. E. Social Bookmarking                      What's this?

The a-Subunit of the V-type H⁺-ATPase Interacts with Phosphofructokinase-1 in Humans^*

Ya Su , Aiwu Zhou , Rafia S. Al-Lamki ¶ and Fiona E. Karet  || **

From the Departments of Medical Genetics, Haematology, ^¶Medicine and ^||Division of Nephrology, Cambridge University, Cambridge CB2 2XY, United Kingdom

V-type or H⁺-ATPases are a family of ATP-dependent proton pumps that move protons across the plasma membrane at specialized sites such as kidney epithelial cells and osteoclasts as well as acidifying intracellular compartments. The 100-kDa polytopic a-subunit of this group of ATPases is suggested to play an important role in coupling the two functions of the pump, ATP hydrolysis and proton transport. In man, different a-subunit isoforms are encoded by four genes. ATP6V0A4 encodes a4, which is expressed apically in -intercalated cells in both human and mouse kidney. We sought binding partners for the C terminus of a4 in order to address its potential role in the H⁺-ATPase complex. Random peptide phage display analysis revealed a consensus motif (WLELRP) with almost complete homology to part of the enzyme phosphofructokinase 1 (PFK-1). Activity of this enzyme is the rate-limiting step in glycolysis. Specificity of a4 binding to this peptide was confirmed by enzyme-linked immunosorbent assay. Protein-protein interaction was further demonstrated by co-immunoprecipitation of a4 with PFK-1 from solubilized human kidney membrane proteins. An in vitro bead-bound PFK-1 pull-down assay showed that this interaction was also true for the ubiquitously expressed a1 subunit. Finally, PFK-1 co-immunolocalized with a4 in -intercalated cells in the collecting ducts of human kidney. These findings indicate a direct link between V-type H⁺-ATPases and glycolysis via the C-terminal region of the a-subunit of the pump and suggest a novel regulatory mechanism between H⁺-ATPase function and energy supply. This interaction between the a-subunit and PFK-1 also provides new evidence that the C terminus of this subunit lies cytoplasmically in vivo.

Received for publication, October 2, 2002 , and in revised form, March 20, 2003.

^* This work was supported by the Wellcome Trust (to Y. S., F. E. K., and A. Z.) and the National Kidney Research Fund (to R. A.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^** To whom correspondence should be addressed: Cambridge Institute for Medical Research, Box 139, Addenbrooke's Hospital, Cambridge, CB2 2XY, UK. Tel.: 44-1223-762617; Fax: 44-1223-331206; E-mail: fek1000{at}cam.ac.uk.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				B. Ediger, S. D. Melman, D. L. Pappas Jr., M. Finch, J. Applen, and K. J. Parra The Tether Connecting Cytosolic (N Terminus) and Membrane (C Terminus) Domains of Yeast V-ATPase Subunit a (Vph1) Is Required for Assembly of V0 Subunit d J. Biol. Chem., July 17, 2009; 284(29): 19522 - 19532. [Abstract] [Full Text] [PDF]

				K. R. Hallows, R. Alzamora, H. Li, F. Gong, C. Smolak, D. Neumann, and N. M. Pastor-Soler AMP-activated protein kinase inhibits alkaline pH- and PKA-induced apical vacuolar H+-ATPase accumulation in epididymal clear cells Am J Physiol Cell Physiol, April 1, 2009; 296(4): C672 - C681. [Abstract] [Full Text] [PDF]

				Y. Su, K. G. Blake-Palmer, S. Sorrell, B. Javid, K. Bowers, A. Zhou, S. H. Chang, S. Qamar, and F. E. Karet Human H+ATPase a4 subunit mutations causing renal tubular acidosis reveal a role for interaction with phosphofructokinase-1 Am J Physiol Renal Physiol, October 1, 2008; 295(4): F950 - F958. [Abstract] [Full Text] [PDF]

				Y. Wang, M. Toei, and M. Forgac Analysis of the Membrane Topology of Transmembrane Segments in the C-terminal Hydrophobic Domain of the Yeast Vacuolar ATPase Subunit a (Vph1p) by Chemical Modification J. Biol. Chem., July 25, 2008; 283(30): 20696 - 20702. [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]

				S. Barone, H. Amlal, M. Kujala, J. Xu, F. Karet, A. Blanchard, J. Kere, and M. Soleimani Regulation of the basolateral chloride/base exchangers AE1 and SLC26A7 in the kidney collecting duct in potassium depletion Nephrol. Dial. Transplant., December 1, 2007; 22(12): 3462 - 3470. [Abstract] [Full Text] [PDF]

				M. Lu, D. Ammar, H. Ives, F. Albrecht, and S. L. Gluck Physical Interaction between Aldolase and Vacuolar H+-ATPase Is Essential for the Assembly and Activity of the Proton Pump J. Biol. Chem., August 24, 2007; 282(34): 24495 - 24503. [Abstract] [Full Text] [PDF]

				A. C. Fry and F. E. Karet Inherited Renal Acidoses Physiology, June 1, 2007; 22(3): 202 - 211. [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]

				S. Padilla-Lopez and D. A. Pearce Saccharomyces cerevisiae Lacking Btn1p Modulate Vacuolar ATPase Activity to Regulate pH Imbalance in the Vacuole J. Biol. Chem., April 14, 2006; 281(15): 10273 - 10280. [Abstract] [Full Text] [PDF]

				P. M. Kane The Where, When, and How of Organelle Acidification by the Yeast Vacuolar H+-ATPase Microbiol. Mol. Biol. Rev., March 1, 2006; 70(1): 177 - 191. [Abstract] [Full Text] [PDF]

				S. Jeyaraj, D. Dakhlallah, S. R. Hill, and B. S. Lee HuR Stabilizes Vacuolar H+-translocating ATPase mRNA during Cellular Energy Depletion J. Biol. Chem., November 11, 2005; 280(45): 37957 - 37964. [Abstract] [Full Text] [PDF]

				Y. Y. Sautin, M. Lu, A. Gaugler, L. Zhang, and S. L. Gluck Phosphatidylinositol 3-Kinase-Mediated Effects of Glucose on Vacuolar H+-ATPase Assembly, Translocation, and Acidification of Intracellular Compartments in Renal Epithelial Cells Mol. Cell. Biol., January 15, 2005; 25(2): 575 - 589. [Abstract] [Full Text] [PDF]

				C. A. Wagner, K. E. Finberg, S. Breton, V. Marshansky, D. Brown, and J. P. Geibel Renal Vacuolar H+-ATPase Physiol Rev, October 1, 2004; 84(4): 1263 - 1314. [Abstract] [Full Text] [PDF]

				F. Blondeau, B. Ritter, P. D. Allaire, S. Wasiak, M. Girard, N. K. Hussain, A. Angers, V. Legendre-Guillemin, L. Roy, D. Boismenu, et al. Tandem MS analysis of brain clathrin-coated vesicles reveals their critical involvement in synaptic vesicle recycling PNAS, March 16, 2004; 101(11): 3833 - 3838. [Abstract] [Full Text] [PDF]

				M. Lu, Y. Y. Sautin, L. S. Holliday, and S. L. Gluck The Glycolytic Enzyme Aldolase Mediates Assembly, Expression, and Activity of Vacuolar H+-ATPase J. Biol. Chem., March 5, 2004; 279(10): 8732 - 8739. [Abstract] [Full Text] [PDF]

				Y.-H. Weng, G. Yang, S. Weiss, and P. A. Dennery Interaction between Heme Oxygenase-1 and -2 Proteins J. Biol. Chem., December 19, 2003; 278(51): 50999 - 51005. [Abstract] [Full Text] [PDF]