Identification of ezrin as a target of gastrin in immature mouse gastric parietal cells

Adelina Pagliocca, Peter Hegyi, Viktoria Venglovecz, Stephen A. Rackstraw, Zara Khan, Galina Burdyga, Timothy C. Wang, Rod Dimaline, Andrea Varro, Graham J. Dockray

Research output: Contribution to journalArticle

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Abstract

The gastric acid-secreting parietal cell exhibits profound morphological changes on stimulation. Studies in gastrin null (Gas-KO) mice indicate that maturation of parietal cell function depends on the hormone gastrin acting at the G-protein-coupled cholecystokinin 2 receptor. The relevant cellular mechanisms are unknown. The application of differential mRNA display to samples of the gastric corpus of wild-type (C57BL/6) and Gas-KO mice identified the cytoskeletal linker protein, ezrin, as a previously unsuspected target of gastrin. Gastrin administered in vivo or added to gastric glands in vitro increased ezrin abundance in Gas-KO parietal cells. In parietal cells of cultured gastric glands from wild-type mice treated with gastrin, histamine or carbachol, ezrin was localized to vesicular structures resembling secretory canaliculi. In contrast, in cultured parietal cells from Gas-KO mice, ezrin was typically distributed in the cytosol, and this did not change after incubation with gastrin, histamine or carbachol. However, priming with gastrin for approximately 24 h, either in vivo prior to cell culture or by addition to cultured gastric glands, induced the capacity for secretagogue-stimulated localization of ezrin to large vesicular structures in Gas-KO mice. Similarly, in a functional assay based on measurement of intracellular pH, cultured parietal cells from Gas-KO mice were refractory to gastrin unless primed. The priming effect of gastrin was not attributable to the paracrine mediator histamine, but was prevented by inhibitors of protein kinase C and transactivation of the epidermal growth factor receptor. We conclude that in gastrin null mice there is reduced ezrin expression and a defect in ezrin subcellular distribution in gastric parietal cells, and that both can be reversed by priming with gastrin.

Original languageEnglish
Pages (from-to)1174-1189
Number of pages16
JournalExperimental Physiology
Volume93
Issue number11
DOIs
Publication statusPublished - Nov 2008

Fingerprint

Gastric Parietal Cells
Gastrins
Gases
Gastric Mucosa
Histamine
Cultured Cells
Carbachol
Plakins
ezrin
Cholecystokinin B Receptor
Gastric Acid
Gene Expression Profiling
GTP-Binding Proteins
Epidermal Growth Factor Receptor
Cytosol
Protein Kinase C
Transcriptional Activation
Stomach

ASJC Scopus subject areas

  • Physiology

Cite this

Identification of ezrin as a target of gastrin in immature mouse gastric parietal cells. / Pagliocca, Adelina; Hegyi, Peter; Venglovecz, Viktoria; Rackstraw, Stephen A.; Khan, Zara; Burdyga, Galina; Wang, Timothy C.; Dimaline, Rod; Varro, Andrea; Dockray, Graham J.

In: Experimental Physiology, Vol. 93, No. 11, 11.2008, p. 1174-1189.

Research output: Contribution to journalArticle

Pagliocca, A, Hegyi, P, Venglovecz, V, Rackstraw, SA, Khan, Z, Burdyga, G, Wang, TC, Dimaline, R, Varro, A & Dockray, GJ 2008, 'Identification of ezrin as a target of gastrin in immature mouse gastric parietal cells', Experimental Physiology, vol. 93, no. 11, pp. 1174-1189. https://doi.org/10.1113/expphysiol.2008.042648
Pagliocca, Adelina ; Hegyi, Peter ; Venglovecz, Viktoria ; Rackstraw, Stephen A. ; Khan, Zara ; Burdyga, Galina ; Wang, Timothy C. ; Dimaline, Rod ; Varro, Andrea ; Dockray, Graham J. / Identification of ezrin as a target of gastrin in immature mouse gastric parietal cells. In: Experimental Physiology. 2008 ; Vol. 93, No. 11. pp. 1174-1189.
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