Chapter 17. Renal V-ATPase: Physiology and Pathophysiology

  1. Masamitsu Futai2,
  2. Yoh Wada3 and
  3. Jack H. Kaplan4
  1. Dennis Brown and
  2. Vladimir Marshansky

Published Online: 6 DEC 2005

DOI: 10.1002/3527606122.ch17

Handbook of ATPases: Biochemistry, Cell Biology, Pathophysiology

Handbook of ATPases: Biochemistry, Cell Biology, Pathophysiology

How to Cite

Brown, D. and Marshansky, V. (2004) Renal V-ATPase: Physiology and Pathophysiology, in Handbook of ATPases: Biochemistry, Cell Biology, Pathophysiology (eds M. Futai, Y. Wada and J. H. Kaplan), Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, FRG. doi: 10.1002/3527606122.ch17

Editor Information

  1. 2

    Division of Biological Sciences, Nanoscience and Nanotechnology Center, Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan

  2. 3

    Division of Biological Sciences, Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan

  3. 4

    University of Illinois at Chicago, Department of Biochemistry and Molecular Genetics, 900 S. Ashland Ave., Chicago, IL 60607, USA

Author Information

  1. Program in Membrane Biology and Renal Unit, Harvard Medical School, Massachusetts General Hospital, Building 149 13th Street, Boston, MA 02129, USA

Publication History

  1. Published Online: 6 DEC 2005
  2. Published Print: 24 JUN 2004

ISBN Information

Print ISBN: 9783527306893

Online ISBN: 9783527606122



  • ATPases;
  • cell biology;
  • pathophysiology of ATPases;
  • compartments;
  • renal V-ATPase;
  • physiology and pathophysiology;
  • distribution of V-ATPase in kidney;
  • regulation of V-ATPase polarity in intercalated cells by acid–base balance;
  • structural organization of V-ATPase in proton secreting cells;
  • acidification of intravesicular compartments by V-ATPase;
  • role of intercalated cell V-ATPase in distal tubule acidosis


This chapter contains sections titled:

  • Introduction

  • Distribution of V-ATPase in the Kidney

    • Proximal Tubule

    • Role of Proton Secretion in Bicarbonate Reabsorption

    • Role of the V-ATPase in Vesicle Recycling in the Proximal Tubule

    • Localization of V-ATPase in the Proximal Tubule

    • Distal Tubule and Loop of Henle

    • Connecting Segment and Collecting Duct

  • Modulation of Intercalated Cell Phenotypes

  • Regulation of V-ATPase Polarity in Intercalated Cells by Acid–Base Balance

    • Modulation of the Intercalated Cell Phenotype

    • Membrane Protein Polarity in Intercalated Cells

  • Structural Organization of the V-ATPase in Proton Secreting Cells

    • Conventional and Immunogold Thin-section Electron Microscopy

    • Rapid-freeze, Deep-etch Imaging of the V-ATPase

  • Acidification of Intravesicular Compartments by the V-ATPase

    • Regulation of V-ATPase Activity and Vesicle Acidification by Protein Interactions

    • Regulation of Acidification by Chloride Channels

  • Physiological Role of Acidification in Proximal Tubule Function

    • Acidification is Required for the Normal Function of Many Intracellular Vesicular Compartments

    • Role of Acidification in Vesicle “Coat” Protein Recruitment

    • V-ATPase a2-Isoform as a Putative pH-sensing Protein

    • Endocytosis and Protein Reabsorption by the Proximal Tubule

    • Normal Albumin Handling by the Proximal Tubule

  • Relationship of Defective Acidification to Proximal Tubule Dysfunction

    • Inherited Fanconi Syndrome – Dent's Disease

    • Perturbation of the Megalin/Cubilin Pathway

    • Acquired Fanconi Syndrome – Cadmium Nephrotoxicity

    • Endocytotic Defect in Polycystic Kidney Disease

    • Endosomal and Lysosomal Acidification in Diabetic Nephropathy

    • Cystinosis is a Lysosomal-dependent Inherited Fanconi Syndrome

  • Role of the Intercalated Cell V-ATPase in Distal Tubule Acidosis

    • Mutations in the B1 (56 kDa) V-ATPase Subunit Cause Distal RTA and Sensorineural Deafness

    • Mutations in the a4 (110 kDa) V-ATPase Subunit Cause Distal RTA

  • Summary

  • Acknowledgments

  • References