Moesin functions antagonistically to the Rho pathway to maintain epithelial integrity
Moesin functions antagonistically to the Rho pathway to maintain epithelial integrity
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DOI：
10.1038/nature01295
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发表时间：
2003-01-02
期刊：
影响因子：
64.8
通讯作者：
Fehon, RG
中科院分区：
文献类型：
--
作者：
Speck, O;Hughes, SC;Fehon, RG
上皮细胞的两个突出特征，顶基极性和高度有序的细胞骨架，取决于与顶端质膜相关的精确定位的蛋白质复合物的存在（1，2），以及调节肌动蛋白组装空间顺序的独立机制（3）。已经提出ERM（埃兹蛋白、根蛋白、膜突蛋白）蛋白将跨膜蛋白连接到顶端结构域中的肌动蛋白细胞骨架（4），表明在上皮细胞中的结构作用，并且它们已经涉及信号传导途径（5）。在这里，我们表明，唯一的果蝇ERM蛋白Moesin功能，以促进皮层肌动蛋白组装和顶端-基底极性。因此，缺乏膜突蛋白的细胞失去上皮特征并采取侵入性迁移行为。我们的数据表明，Moesin促进上皮形态不是通过提供一个基本的结构功能，而是通过拮抗活性的小G T β Rho。因此，膜突蛋白的功能是通过调节细胞信号事件，影响肌动蛋白的组织和极性，维持上皮细胞的完整性。此外，我们的研究结果表明，ERM激活和Rho通路的活性之间存在负反馈。
Two prominent characteristics of epithelial cells, apical-basal polarity and a highly ordered cytoskeleton, depend on the existence of precisely localized protein complexes associated with the apical plasma membrane(1,2), and on a separate machinery that regulates the spatial order of actin assembly(3). ERM (ezrin, radixin, moesin) proteins have been proposed to link transmembrane proteins to the actin cytoskeleton(4) in the apical domain, suggesting a structural role in epithelial cells, and they have been implicated in signalling pathways(5). Here, we show that the sole Drosophila ERM protein Moesin functions to promote cortical actin assembly and apical-basal polarity. As a result, cells lacking Moesin lose epithelial characteristics and adopt invasive migratory behaviour. Our data demonstrate that Moesin facilitates epithelial morphology not by providing an essential structural function, but rather by antagonizing activity of the small GTPase Rho. Thus, Moesin functions in maintaining epithelial integrity by regulating cell-signalling events that affect actin organization and polarity. Furthermore, our results show that there is negative feedback between ERM activation and activity of the Rho pathway.