THE SECRETION-STIMULATED 80K PHOSPHOPROTEIN OF PARIETAL-CELLS IS EZRIN, AND HAS PROPERTIES OF A MEMBRANE CYTOSKELETAL LINKER IN THE INDUCED APICAL MICROVILLI
THE SECRETION-STIMULATED 80K PHOSPHOPROTEIN OF PARIETAL-CELLS IS EZRIN, AND HAS PROPERTIES OF A MEMBRANE CYTOSKELETAL LINKER IN THE INDUCED APICAL MICROVILLI
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DOI：
10.1002/j.1460-2075.1991.tb07775.x
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发表时间：
1991-09-01
期刊：
影响因子：
11.4
通讯作者：
MANGEAT, P
中科院分区：
文献类型：
--
作者：
HANZEL, D;REGGIO, H;MANGEAT, P
在壁细胞中胃酸分泌的刺激涉及质子泵（H，K-ATP酶）从细胞质小管囊泡移位到顶膜以形成长的、含F-肌动蛋白的微绒毛。分泌后，泵被内吞回小管囊泡。因此，壁细胞提供了一个系统的调节膜再循环的研究，与时间上分离的内吞和胞吐步骤。在cAMP介导的刺激过程中，80 kDa的外周膜蛋白在丝氨酸残基上磷酸化。这种蛋白质是一个主要组成部分，连同肌动蛋白和泵，从刺激的细胞分离的顶膜，但不是休息tubulovesicular膜。在此，我们表明胃80 kDa磷蛋白与ezrin密切相关或相同，ezrin是一种蛋白质，其丝氨酸和酪氨酸残基上的磷酸化最近与生长因子诱导培养细胞上的细胞表面结构有关[Bretscher，A.（1989）细胞生物学杂志，108，921-930]。光学和电子显微镜显示，ezrin是与刺激细胞的微绒毛的肌动蛋白丝，但不与在终端网络的细丝。此外，大量埃兹蛋白存在于静息和刺激细胞的基底外侧膜内折叠中。提取研究表明，ezrin是一种细胞骨架蛋白在未刺激和刺激的细胞，它的协会与细胞骨架在刺激的细胞更稳定。这些研究表明，埃兹蛋白是一种膜细胞骨架的连接器，可能发挥关键作用，在控制组装的分泌顶端微绒毛在壁细胞，并最终在调节酸分泌。与早期的研究一起，我们认为ezrin可能是一个通用的底物激酶参与调节肌动蛋白含细胞表面结构。
Stimulation of gastric acid secretion in parietal cells involves the translocation of the proton pump (H,K-ATPase) form cytoplasmic tubulovesicles to the apical membrane to form long, F-actin-containing, microvilli. Following secretion, the pump is endocytosed back into tubulovesicles. The parietal cell therefore offers a system for the study of regulated membrane recycling, with temporally separated endocytic and exocytic steps. During cAMP-mediated stimulation, an 80 kDa peripheral membrane protein becomes phosphorylated on serine residues. This protein is a major component, together with actin and the pump, of the isolated apical membrane from stimulated cells, but not the resting tubulovesicular membrane. Here we show that the gastric 80 kDa phosphoprotein is closely related or identical to ezrin, a protein whose phosphorylation on serine and tyrosine residues was recently implicated in the induction by growth factors of cell surface structures on cultured cells [Bretscher, A. (1989) J. Cell Biol., 108, 921-930]. Light and electron microscopy reveal that ezrin is associated with the actin filaments of the microvilli of stimulated cells, but not with the filaments in the terminal web. In addition, a Significant amount of ezrin is present in the basolateral membrane infoldings of both resting and stimulated cells. Extraction studies show that ezrin is a cytoskeletal protein in unstimulated and stimulated cells, and its association with the cytoskeleton is more stable in stimulated cells. These studies indicate that ezrin is a membrane cytoskeletal linker that may play a key role in the control of the assembly of secretory apical microvilli in parietal cells and ultimately in the regulation of acid secretion. Taken together with the earlier studies, we suggest that ezrin might be a general substrate for kinases involved in the regulation of actin-containing cell surface structures.