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Hip1r is expressed in gastric parietal cells and is required for tubulovesicle formation and cell survival in mice
Renu N. Jain, … , Catherine S. Chew, Linda C. Samuelson
Renu N. Jain, … , Catherine S. Chew, Linda C. Samuelson
Published June 5, 2008
Citation Information: J Clin Invest. 2008;118(7):2459-2470. https://doi.org/10.1172/JCI33569.
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Research Article Cell biology

Hip1r is expressed in gastric parietal cells and is required for tubulovesicle formation and cell survival in mice

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Abstract

Huntingtin interacting protein 1 related (Hip1r) is an F-actin– and clathrin-binding protein involved in vesicular trafficking. In this study, we demonstrate that Hip1r is abundantly expressed in the gastric parietal cell, predominantly localizing with F-actin to canalicular membranes. Hip1r may provide a critical function in vivo, as demonstrated by extensive changes to parietal cells and the gastric epithelium in Hip1r-deficient mice. Electron microscopy revealed abnormal apical canalicular membranes and loss of tubulovesicles in mutant parietal cells, suggesting that Hip1r is necessary for the normal trafficking of these secretory membranes. Accordingly, acid secretory dynamics were altered in mutant parietal cells, with enhanced activation and acid trapping, as measured in isolated gastric glands. At the whole-organ level, gastric acidity was reduced in Hip1r-deficient mice, and the gastric mucosa was grossly transformed, with fewer parietal cells due to enhanced apoptotic cell death and glandular hypertrophy associated with cellular transformation. Hip1r-deficient mice had increased expression of the gastric growth factor gastrin, and mice mutant for both gastrin and Hip1r exhibited normalization of both proliferation and gland height. Taken together, these studies demonstrate that Hip1r plays a significant role in gastric physiology, mucosal architecture, and secretory membrane dynamics in parietal cells.

Authors

Renu N. Jain, Asma A. Al-Menhali, Theresa M. Keeley, Jianhua Ren, Mohammed El-Zaatari, Xunsheng Chen, Juanita L. Merchant, Theodora S. Ross, Catherine S. Chew, Linda C. Samuelson

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Figure 3

Parietal cells from Hip1r-deficient mice do not contain tubulovesicles.

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Parietal cells from Hip1r-deficient mice do not contain tubulovesicles.
...
Transmission EM was used to examine parietal cell ultrastructure in 2-month-old WT (A–D) and Hip1r-deficient (E–H) mice. Mice were fasted overnight, with or without histamine treatment to stimulate acid, and tissues were processed to assess resting (A, B, E, and F) and stimulated (C, D, G, and H) vesicular structure. Note the absence of tubulovesicles in resting Hip1r-deficient cells (E and F), which is similar to stimulated WT cells (C and D). TV, tubulovesicles; N, nucleus. Scale bars: 2 μm (white, A, C, E, and G; black, B, D, F, and H).

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