A tyrosine-based signal targets H/K-ATPase to a regulated compartment and is required for the cessation of gastric acid secretion

N Courtois-Coutry; D Roush; V Rajendran; J B McCarthy; J Geibel; M Kashgarian; M J Caplan

doi:10.1016/s0092-8674(00)80510-3

A tyrosine-based signal targets H/K-ATPase to a regulated compartment and is required for the cessation of gastric acid secretion

Cell. 1997 Aug 8;90(3):501-10. doi: 10.1016/s0092-8674(00)80510-3.

Authors

N Courtois-Coutry¹, D Roush, V Rajendran, J B McCarthy, J Geibel, M Kashgarian, M J Caplan

Affiliation

¹ Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.

PMID: 9267030
DOI: 10.1016/s0092-8674(00)80510-3

Abstract

Gastric acid secretion is mediated by the H/K-ATPase of parietal cells. Activation of acid secretion involves insertion of H/K-ATPase into the parietal cell plasmalemma, while its cessation is associated with reinternalization of the H/K-ATPase into an intracellular storage compartment. The cytoplasmic tail of the H/K-ATPase beta subunit includes a four residue sequence homologous to tyrosine-based endocytosis signals. We generated transgenic mice expressing H/K-ATPase beta subunit in which this motif's tyrosine residue is mutated to alanine. Gastric glands from animals expressing mutant beta subunit constitutively secrete acid and continuously express H/K-ATPase at their cell surfaces. Thus, the beta subunit's tyrosine-based signal is required for the internalization of H/K-ATPase and for the termination of acid secretion. As a consequence of chronic hyperacidity, the mice develop gastric ulcers and a hypertrophic gastropathy resembling Menetrier's disease.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Animals
COS Cells
Calcium / metabolism
Cytomegalovirus / genetics
DNA Primers
Endocytosis
Gastric Acid / metabolism*
Gastric Mucosa / cytology
Gastric Mucosa / enzymology
H(+)-K(+)-Exchanging ATPase / biosynthesis
H(+)-K(+)-Exchanging ATPase / chemistry
H(+)-K(+)-Exchanging ATPase / metabolism*
Macromolecular Substances
Mice
Mice, Transgenic
Microscopy, Immunoelectron
Mutagenesis, Site-Directed
Parietal Cells, Gastric / enzymology
Parietal Cells, Gastric / physiology*
Parietal Cells, Gastric / ultrastructure
Polymerase Chain Reaction
Promoter Regions, Genetic
Recombinant Proteins / biosynthesis
Recombinant Proteins / chemistry
Recombinant Proteins / metabolism
Signal Transduction*
Transfection
Tyrosine*

Substances

DNA Primers
Macromolecular Substances
Recombinant Proteins
Tyrosine
H(+)-K(+)-Exchanging ATPase
Calcium