Yoshida Saori, Yamamoto Hiroto, Tetsui Takahito, Kobayakawa Yuka, Hatano Ryo, Mukaisho Ken-ichi, Hattori Takanori, Sugihara Hiroyuki, Asano Shinji
Department of Molecular Physiology, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Noji-Higashi, Kusatsu, Shiga, 525-8577, Japan.
Department of Pathology, Shiga University of Medical Sciences, Seta Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan.
J Physiol Sci. 2016 Jan;66(1):53-65. doi: 10.1007/s12576-015-0393-4. Epub 2015 Sep 2.
Ezrin, an adaptor protein that cross-links plasma membrane-associated proteins with the actin cytoskeleton, is concentrated on apical surfaces of epithelial cells, especially in microvilli of the small intestine and stomach. In the stomach, ezrin is predominantly expressed on the apical canalicular membrane of parietal cells. Transgenic ezrin knockdown mice in which the expression level of ezrin was reduced to <7% compared with the wild-type suffered from achlorhydria because of impairment of membrane fusion between tubulovesicles and apical membranes. We observed, for the first time, hypergastrinemia and foveolar hyperplasia in the gastric fundic region of the knockdown mice. Dilation of fundic glands was observed, the percentage of parietal and chief cells was reduced, and that of mucous-secreting cells was increased. The parietal cells of knockdown mice contained dilated tubulovesicles and abnormal mitochondria, and subsets of these cells contained abnormal vacuoles and multilamellar structures. Therefore, lack of ezrin not only causes achlorhydria and hypergastrinemia but also changes the structure of gastric glands, with severe perturbation of the secretory membranes of parietal cells.
埃兹蛋白是一种将质膜相关蛋白与肌动蛋白细胞骨架交联的衔接蛋白，集中在上皮细胞的顶端表面，特别是在小肠和胃的微绒毛中。在胃中，埃兹蛋白主要表达于壁细胞的顶端小管膜上。与野生型相比，埃兹蛋白表达水平降低至<7%的转基因埃兹蛋白敲低小鼠因微管泡与顶端膜之间的膜融合受损而患有无胃酸症。我们首次在敲低小鼠的胃底区域观察到高胃泌素血症和胃小凹增生。观察到胃底腺扩张，壁细胞和主细胞的百分比降低，而分泌黏液细胞的百分比增加。敲低小鼠的壁细胞含有扩张的微管泡和异常线粒体，其中一部分细胞含有异常液泡和多层结构。因此，缺乏埃兹蛋白不仅会导致无胃酸症和高胃泌素血症，还会改变胃腺的结构，严重扰乱壁细胞的分泌膜。
