Max-Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Max-Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
J Cell Sci. 2019 Aug 7;132(15):jcs228338. doi: 10.1242/jcs.228338.
During morphogenesis, epithelia undergo dynamic rearrangements, which requires continuous remodelling of junctions and cell shape, but at the same time mechanisms preserving cell polarity and tissue integrity. Apico-basal polarity is key for the localisation of the machinery that enables cell shape changes. The evolutionarily conserved Crumbs protein is critical for maintaining apico-basal polarity and epithelial integrity. How Crumbs is maintained in a dynamically developing embryo remains largely unknown. Here, we applied quantitative fluorescence techniques to show that, during germ band retraction, Crumbs dynamics correlates with the morphogenetic activity of the epithelium. Genetic and pharmacological perturbations revealed that the mobile pool of Crumbs is fine-tuned by the actomyosin cortex in a stage-dependent manner. Stabilisation of Crumbs at the plasma membrane depends on a proper link to the actomyosin cortex via an intact FERM-domain-binding site in its intracellular domain, loss of which leads to increased junctional tension and higher E-cadherin (also known as Shotgun) turnover, resulting in impaired junctional rearrangements. These data define Crumbs as a mediator between polarity and junctional regulation to orchestrate epithelial remodelling in response to changes in actomyosin activity.This article has an associated First Person interview with the first author of the paper.
在形态发生过程中，上皮细胞经历动态重排，这需要不断重塑连接和细胞形状，但同时也要保持细胞极性和组织完整性的机制。顶底极性对于定位使细胞形状发生变化的机制至关重要。进化上保守的 Crumbs 蛋白对于维持顶底极性和上皮完整性至关重要。Crumbs 如何在动态发育的胚胎中保持稳定在很大程度上仍然未知。在这里，我们应用定量荧光技术表明，在生殖带缩回期间，Crumbs 的动力学与上皮的形态发生活性相关。遗传和药理学扰动表明，肌动球蛋白皮层以依赖于阶段的方式精细调节 Crumbs 的可移动池。Crumbs 在质膜上的稳定取决于其细胞内结构域中完整的 FERM 结构域结合位点与肌动球蛋白皮层的适当连接，该结合位点的缺失会导致连接张力增加和 E-钙粘蛋白（也称为 Shotgun）周转率增加，从而导致连接重排受损。这些数据将 Crumbs 定义为极性和连接调节之间的介质，以协调上皮重塑以响应肌动球蛋白活性的变化。本文有一篇与论文第一作者的第一人称访谈。
