Insights Into the Cell Biology, Development and Pathology of the Gastric Mucosa Revealed in Gastric H/K ATPase and Gastrin-Deficient Mice

  • Ian R. Van Driel
  • Teo V. Franic
  • Louise M. Judd
  • Simon P. Barrett
  • Katrina L. Scarff
  • Linda C. Samuelson
  • Paul A. Gleeson

Abstract

The gastric H+/K+-ATPase, present in gastric parietal (oxyntic) cells, exchanges luminal K+ for cytoplasmic H+ and is the enzyme principally responsible for gastric luminal acidification (6, 25, 32). The gastric H+/K+-ATPase is composed of two non-covalently linked subunits, an α (H/Kα) and a β (H/Kβ), with apparent molecular weights of 95 kDa and 60–90 kDa, respectively (1, 25). H/Kα (encoded by the mouse gene Atp4a) contains the catalytic sites of the enzyme and has 10 transmembrane domains. The highly glycosylated H/Kβ_(2, 31)(encoded by the mouse gene Atp4b) has one transmembrane domain (30), is required for the transport of an active enzyme complex from the ER to apical membranes (9, 11), and for gastric acid secretion (26). More detail on the structure and function of the gastric H/K ATPase subunits is supplied elsewhere in this volume.

Keywords

Codon Adenosine Luminal Eosin Galactose 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Besancon, M., J. Shin, F. Mercier, K. Munson, M. Miller, S. Hersey, and G. Sachs. Membrane topology and omeprazole labeling of the gastric H+,K+-adenosine triphosphatase. Biochemistry 32: 2345–55, 1993.PubMedCrossRefGoogle Scholar
  2. 2.
    Callaghan, J. M., B. H. Toh, J. M. Pettitt, D. C. Humphris, and P. A. Gleeson. Poly-N-acetyllactosamine-specifc tomato lectin interacts with gastric parietal cells: Identification of a tomato-lectin binding 60-90x103 Mr membrane glycoprotein of tubulovesicles. J. Cell Sci. 95: 563–576,1990.PubMedGoogle Scholar
  3. 3.
    Canfield, V., A. B. West, J. R. Goldenring, and R. Levenson. Genetic ablation of parietal cells in transgenic mice: A new model for analyzing cell lineage relationships in the gastric mucosa. Proc.Natl Acad.Sci.USA 93: 2431–2435, 1996.PubMedCrossRefGoogle Scholar
  4. 4.
    Courtois-Coutry, N., D. Roush, V. Rajendran, J. McCarthy, J. Geibel, M. Kashgarian, and M. Caplan. A tyrosine-based signal targets H/K-ATPase to a regulated compartment and is required for the cessation of gastric acid secretion. Cell 90: 501–10, 1997.PubMedCrossRefGoogle Scholar
  5. 5.
    Forte, J. G., B. Ly, Q. Rong, S. Ogihara, M. Ramilo, B. Agnew, and X. Yao. State of actin in gastric parietal cells. Am. J. Physiology 274: C97–104, 1998.Google Scholar
  6. 6.
    Forte, J. G., and X. B. Yao. The membrane-recruitment-and-recycling hypothesis of gastric HCl secretion. Trends Cell Biol. 6: 45–48, 1996.PubMedCrossRefGoogle Scholar
  7. 7.
    Franic, T. V., L. M. Judd, D. Robinson, S. P. Barrett, K. L. Scarff, P. A. Gleeson, L. C. Samuelson, and I. R. van Driel. Regulation of gastric epithelial cell development revealed in H+/K+ ATPase β subunit- and gastrin-deficient mice. American Journal of Physiology (Gastrointestinal and Liver) 281: G1502–G1511, 2001.PubMedGoogle Scholar
  8. 8.
    Friis-Hansen, L., F. Sundler, Y. Li, P. J. Gillespie, T. L. Saunders, J. K. Greenson, C. Owyang, J. F. Rehfeld, and L. C. Samuelson, Impaired gastric acid secretion in gastrin-deficient mice. Am. J. Physiol. 274: G561–8, 1998.PubMedGoogle Scholar
  9. 9.
    Gottardi, C. J., and M. J. Caplan. An Ion-Transporting ATPase Encodes Multiple Apical Localization Signals. J. Cell Biol 121: 283–293, 1993.PubMedCrossRefGoogle Scholar
  10. 10.
    Hanzel, D., H. Reggio, A. Bretscher, J. Forte, and P. Mangeat. The secretion-stimulated 80K phosphoprotein of parietal cells is ezrin, and has properties of a membrane cytoskeletal linker in the induced apical microvilli. EMBO J 10: 2363–2373, 1991.PubMedGoogle Scholar
  11. 11.
    Horisberger, J.-D., P. Jaunin, M. A. Reuben, L. S. Lasater, D. C. Chow, J. G. Forte, G. Sachs, B. C. Rossier, and K. Geering. The H,K-ATPase β subunit can act as a surrogate for the α subunit of Na,K pumps. J.Biol. Chem. 266: 19131–19134, 1991.PubMedGoogle Scholar
  12. 12.
    Ito, S. Functional Gastric Morphology. New York: Raven Press, 1987.Google Scholar
  13. 13.
    Jaunin, P., F. Jaisser, A. T. Beggah, K. Takeyasu, P. Mangeat, B. C. Rossier, J. D. Horisberger, and K. Geering. Role of the Transmembrane and Extracytoplas-mic Domain of β-Subunits in Subunit Assembly, Intracellular Transport, and Functional Expression of Na,K-Pumps. J.Cell Biol 123: 1751–1759, 1993.PubMedCrossRefGoogle Scholar
  14. 14.
    Judd, L. M., P. A. Gleeson, B. H. Toh, and I. R. van Driel. Autoimmune gastritis results in disruption of gastric epithelial cell development. Am. J. Physiol Gastointest. Liver Physiol 277: G209–G218, 1999.Google Scholar
  15. 15.
    Karam, S., and C. Leblond. Dynamics of epithelial cells in the corpus of the mouse stomach. I. Identification of proliferative cell types and pinpointing of the stem cell. Anatomical Record 236: 259–79, 1993.PubMedCrossRefGoogle Scholar
  16. 16.
    Karam, S. M. New insights into the stem cells and the precursors of the gastric epithelium. Nutrition. 11: 607–613, 1995.PubMedGoogle Scholar
  17. 17.
    Karam, S. M., and J. G. Forte. Inhibiting gastric H(+)-K(+)-ATPase activity by omeprazole promotes degeneration and production of parietal cells. Am J Physiol 266: G745–58, 1994.PubMedGoogle Scholar
  18. 18.
    Konda, Y., H. Kamimura, H. Yokota, N. Hayashi, K. Sugano, and T. Takeuchi. Gastrin stimulates the growth of gastric pit with less-differentiated features. Am. J. Physiol 277: G773–84, 1999.PubMedGoogle Scholar
  19. 19.
    Lee, A., J. O’Rourke, M. C. De Ungria, B. Robertson, G. Daskalopoulos, and M. F. Dixon. A standardized mouse model of Helicobacter pylori infection: introducing the Sydney strain. Gastroenterology 112: 1386–97., 1997.PubMedCrossRefGoogle Scholar
  20. 20.
    Li, Q., S. Karam, and J. Gordon. Simian virus 40 T antigen-induced amplification of pre-parietal cells in transgenic mice. Effects on other gastric epithelial cell lineages and evidence for a p53-independent apoptotic mechanism that operates in a committed progenitor. Journal of Biological Chemistry 270: 15777–88, 1995.PubMedCrossRefGoogle Scholar
  21. 21.
    Li, Q. T., S. M. Karam, and J. I. Gordon. Diphtheria toxin-mediated ablation of parietal cells in the stomach of transgenic mice. J.Biol.Chem. 271: 3671–3676, 1996.PubMedCrossRefGoogle Scholar
  22. 22.
    Pettitt, J. M., D. C. Humphris, S. P. Barrett, B. H. Toh, I. R. van Driel, and P. A. Gleeson. Fast freeze-fixation/freeze-substitution reveals the secretory membranes of the gastric parietal cell as a network of helically coiled tubule — A new model for parietal cell transformation. J.Cell Sci. 108: 1127–1141, 1995.PubMedGoogle Scholar
  23. 23.
    Pettitt, J. M., B. H. Toh, J. M. Callaghan, P. A. Gleeson, and I. R. van Driel. Gastric Parietal Cell Development — Expression of the H+/K+ ATPase Subunits Coincides with the Biogenesis of the Secretory Membranes. Immun. Cell Biol. 71: 191–200, 1993.CrossRefGoogle Scholar
  24. 24.
    Pettitt, J. M., I. R. van Driel, B. H. Toh, and P. A. Gleeson. From coiled tubules to a secretory canaliculus: A new model for membrane transformation and acid secretion by gastric parietal cells. Tr. Cell Biol. 6: 49–53, 1996.CrossRefGoogle Scholar
  25. 25.
    Sachs, G. The gastric H,K ATPase — Regulation and structure/function of the acid pump of the stomach. In: Physiology of the Gastrointestinal Tract (3rd ed.), edited by L. R. Johnson. New York: Raven, 1994, p. 1119–1138.Google Scholar
  26. 26.
    Scarff, K. L., L. M. Judd, B. H. Toh, P. A. Gleeson, and I. R. van Driel. Gastric H002B/K+-Adenosine triphosphatase β subunit is required for normal function, development, and membrane structure of mouse parietal cells. Gastroenterology 117: 605–618, 1999.PubMedCrossRefGoogle Scholar
  27. 27.
    Schultheis, P. J., L. L. Clarke, P. Meneton, M. Harline, G. P. Boivin, G. Stemmermann, J. J. Duffy, T. Doetschman, M. L. Miller, and G. E. Shull. Targeted disruption of the murine Na+/H+ exchanger isoform 2 gene causes reduced viability of gastric parietal cells and loss of net acid secretion. Journal of Clinical Investigation 101: 1243–53, 1998.PubMedCrossRefGoogle Scholar
  28. 28.
    Scott, D., H. Helander, S. Hersey, and G. Sachs. The site of acid secretion in the mammalian parietal cell. Biochim Biophys Acta 1146: 73–80, 1993.PubMedCrossRefGoogle Scholar
  29. 29.
    Spicer, Z., M. L. Miller, A. Andringa, T. M. Riddle, J. J. Duffy, T. Doetschman, and G. E. Shull. Stomachs of mice lacking the gastric H,K-ATPase alpha-subunit have achlorhydria, abnormal parietal cells, and ciliated metaplasia. Journal of Biological Chemistry 275: 21555–21565, 2000.PubMedCrossRefGoogle Scholar
  30. 30.
    Toh, B. H., P. A. Gleeson, R. J. Simpson, R. L. Moritz, J. Callaghan, I. Goldkorn, C. M. Jones, T. M. Martinelli, F. T. Mu, D. C. Humphris, J. M. Pettitt, Y. Mori, T. Masuda, P. Sobieszczuk, J. Weinstock, T. Mantamadiotis, and G. S. Baldwin. The 60–90 kDa parietal cell autoantigen associated with autoimmune gastritis is a β subunit of the gastric H+K+-ATPase (proton pump). Proc. Natl Acad. Sci. U.S.A. 87: 6418–6422, 1990.PubMedCrossRefGoogle Scholar
  31. 31.
    Tyagarajan, K., R. R. Townsend, and J. G. Forte. The beta-subunit of the rabbit H,K-ATPase: A glycoprotein with all terminal lactosamine units capped with alpha-linked galactose residues. Biochemistry 35: 3238–3246, 1996.PubMedCrossRefGoogle Scholar
  32. 32.
    van Driel, I. R., and J. M. Callaghan. Proton and potassium transport by H+/K(+)-ATPases. Clin Exp Pharmacol Physiol 22: 952–60, 1995.PubMedCrossRefGoogle Scholar
  33. 33.
    Wang, T. C., and G. J. Dockray. Lessons from genetically engineered animal models. I. Physiological studies with gastrin in transgenic mice. Am J Physiol 217: G6–11, 1999.Google Scholar
  34. 34.
    Wang, T. C., T. J. Koh, A. Varro, R. J. Cahill, C. A. Dangler, J. G. Fox, and G. J. Dockray. Processing and proliferative effects of human progastrin in transgenic mice. J. Clin. Invest. 98: 1918–29, 1996.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Ian R. Van Driel
    • 1
  • Teo V. Franic
    • 1
  • Louise M. Judd
    • 2
  • Simon P. Barrett
    • 3
  • Katrina L. Scarff
    • 4
  • Linda C. Samuelson
    • 5
  • Paul A. Gleeson
    • 1
  1. 1.The Russell Grimwade School of Biochemistry and Molecular BiologyThe University of MelbourneMelbourneAustralia
  2. 2.Department of Molecular Genetics, Biochemistry and MicrobiologyUniversity of CincinnatiCincinnatiUSA
  3. 3.Department of Pathology and ImmunologyMonash University Medical School, Alfred HospitalMelbourneAustralia
  4. 4.Current address: Department of Biochemistry and Molecular BiologyMonash UniversityClayton, MelbourneAustralia
  5. 5.Department of PhysiologyThe University of MichiganAnn ArborUSA

Personalised recommendations