Deletion of the chloride transporter Slc26a9 causes loss of tubulovesicles in parietal cells and impairs acid secretion in the stomach. Proc Natl Acad Sci U S A 2008 Nov 18;105(46):17955-60
Date
11/14/2008Pubmed ID
19004773Pubmed Central ID
PMC2582584DOI
10.1073/pnas.0800616105Scopus ID
2-s2.0-56649086776 (requires institutional sign-in at Scopus site) 91 CitationsAbstract
Slc26a9 is a recently identified anion transporter that is abundantly expressed in gastric epithelial cells. To study its role in stomach physiology, gene targeting was used to prepare mice lacking Slc26a9. Homozygous mutant (Slc26a9(-/-)) mice appeared healthy and displayed normal growth. Slc26a9 deletion resulted in the loss of gastric acid secretion and a moderate reduction in the number of parietal cells in mutant mice at 5 weeks of age. Immunofluorescence labeling detected the H-K-ATPase exclusively on the apical pole of gastric parietal cells in Slc26a9(-/-) mice, in contrast to the predominant cytoplasmic localization in Slc26a9(+/+) mice. Light microscopy indicated that gastric glands were dilated, and electron micrographs displayed a distinct and striking absence of tubulovesicles in parietal cells and reductions in the numbers of parietal and zymogen cells in Slc26a9(-/-) stomach. Expression studies indicated that Slc26a9 can function as a chloride conductive pathway in oocytes as well as a Cl(-)/HCO(3)(-) exchanger in cultured cells, and localization studies in parietal cells detected its presence in tubulovesicles. We propose that Slc26a9 plays an essential role in gastric acid secretion via effects on the viability of tubulovesicles/secretory canaliculi and by regulating chloride secretion in parietal cells.
Author List
Xu J, Song P, Miller ML, Borgese F, Barone S, Riederer B, Wang Z, Alper SL, Forte JG, Shull GE, Ehrenfeld J, Seidler U, Soleimani MAuthor
Jesse Ehrenfeld MD, MPH Sr Associate Dean, Director, Professor in the Advancing a Healthier Wisconsin Endowment department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Newborn
Anion Transport Proteins
Antiporters
Biomarkers
COS Cells
Cell Membrane
Fluorescent Antibody Technique
Gastric Acid
Gene Deletion
H(+)-K(+)-Exchanging ATPase
Hydrogen-Ion Concentration
Immunoblotting
Mice
Mice, Knockout
Parietal Cells, Gastric
SLC4A Proteins
Titrimetry
Xenopus