Published online 4 April 2005. doi:10.1083/jcb.200410083
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 169, Number 1, 21-28
Achlorhydria by ezrin knockdown
:
defects in the formation/expansion of apical canaliculi in gastric parietal cells
Atsushi Tamura1,
Shojiro Kikuchi1,2,
Masaki Hata3,
Tatsuya Katsuno1,
Takeshi Matsui3,
Hisayoshi Hayashi4,
Yuichi Suzuki4,
Tetsuo Noda5,6,
Shoichiro Tsukita1, and
Sachiko Tsukita1,7
1 Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
2 Department of Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan
3 KAN Research Institute, Kyoto Research Park, Shimogyo-ku, Kyoto 606-8317, Japan
4 Laboratory of Physiology, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, Japan
5 Department of Cell Biology, Cancer Institute of Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan
6 Department of Molecular Genetics, Tohoku University School of Medicine, Seryo-cho, Aoba-ku, Sendai 980-8575, Japan
7 School of Health Sciences, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan
Correspondence to Sachiko Tsukita: atsukita{at}mfour.med.kyoto-u.ac.jp
Abstract
Loss of gastric acid secretion is pathologically known as achlorhydria. Acid-secreting parietal cells are characterized by abundant expression of ezrin (Vil2), one of ezrin/radixin/moesin proteins, which generally cross-link actin filaments with plasma membrane proteins. Here, we show the direct in vivo involvement of ezrin in gastric acid secretion. Ezrin knockout (Vil2/) mice did not survive >1.5 wk after birth, making difficult to examine gastric acid secretion. We then generated ezrin knockdown (Vil2kd/kd) mice by introducing a neomycin resistance cassette between exons 2 and 3. Vil2kd/kd mice born at the expected Mendelian ratio exhibited growth retardation and a high mortality. Approximately 7% of Vil2kd/kd mice survived to adulthood. Ezrin protein levels in Vil2kd/kd stomachs decreased to <5% of the wild-type levels without compensatory up-regulation of radixin or moesin. Adult Vil2kd/kd mice suffered from severe achlorhydria. Immunofluorescence and electron microscopy revealed that this achlorhydria was caused by defects in the formation/expansion of canalicular apical membranes in gastric parietal cells.
Abbreviations used in this paper: ERM, ezrin/radixin/moesin; HCl, hydrochloric acid.

CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
This article has been cited by other articles:
-
Alexander, R. T., Grinstein, S.
(2009). Tethering, recycling and activation of the epithelial sodium-proton exchanger, NHE3. J. Exp. Biol.
212: 1630-1637
[Abstract]
[Full Text]
-
Wakayama, T., Nakata, H., Kurobo, M., Sai, Y., Iseki, S.
(2009). Expression, Localization, and Binding Activity of the Ezrin/Radixin/Moesin Proteins in the Mouse Testis. J. Histochem. Cytochem.
57: 351-362
[Abstract]
[Full Text]
-
Sadakata, H., Okazawa, H., Sato, T., Supriatna, Y., Ohnishi, H., Kusakari, S., Murata, Y., Ito, T., Nishiyama, U., Minegishi, T., Harada, A., Matozaki, T.
(2009). SAP-1 is a microvillus-specific protein tyrosine phosphatase that modulates intestinal tumorigenesis. GENES CELLS
14: 295-308
[Abstract]
[Full Text]
-
Zhu, L., Hatakeyama, J., Zhang, B., Makdisi, J., Ender, C., Forte, J. G.
(2009). Novel insights of the gastric gland organization revealed by chief cell specific expression of moesin. Am. J. Physiol. Gastrointest. Liver Physiol.
296: G185-G195
[Abstract]
[Full Text]
-
Pagliocca, A., Hegyi, P., Venglovecz, V., Rackstraw, S. A., Khan, Z., Burdyga, G., Wang, T. C., Dimaline, R., Varro, A., Dockray, G. J.
(2008). Identification of ezrin as a target of gastrin in immature mouse gastric parietal cells. Exp Physiol
93: 1174-1189
[Abstract]
[Full Text]
-
Wang, F., Xia, P., Wu, F., Wang, D., Wang, W., Ward, T., Liu, Y., Aikhionbare, F., Guo, Z., Powell, M., Liu, B., Bi, F., Shaw, A., Zhu, Z., Elmoselhi, A., Fan, D., Cover, T. L., Ding, X., Yao, X.
(2008). Helicobacter pylori VacA Disrupts Apical Membrane-Cytoskeletal Interactions in Gastric Parietal Cells. J. Biol. Chem.
283: 26714-26725
[Abstract]
[Full Text]
-
Zhu, L., Hatakeyama, J., Chen, C., Shastri, A., Poon, K., Forte, J. G.
(2008). Comparative study of ezrin phosphorylation among different tissues: more is good; too much is bad. Am. J. Physiol. Cell Physiol.
295: C192-C202
[Abstract]
[Full Text]
-
D'Angelo, R., Aresta, S., Blangy, A., Del Maestro, L., Louvard, D., Arpin, M.
(2007). Interaction of Ezrin with the Novel Guanine Nucleotide Exchange Factor PLEKHG6 Promotes RhoG-dependent Apical Cytoskeleton Rearrangements in Epithelial Cells. Mol. Biol. Cell
18: 4780-4793
[Abstract]
[Full Text]
-
Zhu, L., Zhou, R., Mettler, S., Wu, T., Abbas, A., Delaney, J., Forte, J. G.
(2007). High turnover of ezrin T567 phosphorylation: conformation, activity, and cellular function. Am. J. Physiol. Cell Physiol.
293: C874-C884
[Abstract]
[Full Text]
-
Dimaline, R., Varro, A.
(2007). Attack and defence in the gastric epithelium - a delicate balance. Exp Physiol
92: 591-601
[Abstract]
[Full Text]
-
Chiba, H., Sakai, N., Murata, M., Osanai, M., Ninomiya, T., Kojima, T., Sawada, N.
(2006). The nuclear receptor hepatocyte nuclear factor 4{alpha} acts as a morphogen to induce the formation of microvilli. JCB
175: 971-980
[Abstract]
[Full Text]
-
Sawaguchi, A., Aoyama, F., Ohashi, M., Ide, S., Suganuma, T.
(2006). Ultrastructural transformation of gastric parietal cells reverting from the active to the resting state of acid secretion revealed in isolated rat gastric mucosa model processed by high-pressure freezing. J Electron Microsc (Tokyo)
55: 97-105
[Abstract]
[Full Text]
-
Zhou, R., Zhu, L., Kodani, A., Hauser, P., Yao, X., Forte, J. G.
(2005). Phosphorylation of ezrin on threonine 567 produces a change in secretory phenotype and repolarizes the gastric parietal cell. J. Cell Sci.
118: 4381-4391
[Abstract]
[Full Text]