A molecular mechanotransduction pathway regulates collective migration of epithelial cells
A molecular mechanotransduction pathway regulates collective migration of epithelial cells
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DOI：
10.1038/ncb3115
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发表时间：
2015-03-01
影响因子：
21.3
通讯作者：
Spatz, Joachim P.
中科院分区：
文献类型：
--
作者：
Das, Tamal;Safferling, Kai;Spatz, Joachim P.
上皮细胞的集体运动在包括胚胎形态发生、癌症和伤口愈合在内的各种基本生理过程中驱动必要的多细胞组织。然而，确保许多细胞协调运动的分子机制仍然难以捉摸。在这里，我们展示了一种肿瘤抑制蛋白，merlin，通过作为机械化学传感器来协调数十个细胞的集体迁移。在固定的上皮单层和三维人体皮肤中，梅林定位于皮质细胞-细胞连接处。在迁移开始时，一部分皮层梅林重新定位到细胞质中。这种重新定位是由前导细胞的细胞间拉力触发的，并取决于基于肌动球蛋白的细胞收缩性。然后，在迁移细胞中，根据细胞间拉力的提示，显示长距离排序，merlin坐标在多细胞长度尺度上极化Rac1激活和片层基形成。总之，这些结果提供了一种独特的分子机制，将细胞间力与迁移上皮中的集体细胞运动联系起来。
Collective movement of epithelial cells drives essential multicellular organization during various fundamental physiological processes encompassing embryonic morphogenesis, cancer and wound healing. Yet the molecular mechanism that ensures the coordinated movement of many cells remains elusive. Here we show that a tumour suppressor protein, merlin, coordinates collective migration of tens of cells, by acting as a mechanochemical transducer. In a stationary epithelial monolayer and also in three-dimensional human skin, merlin localizes to cortical cell-cell junctions. During migration initiation, a fraction of cortical merlin relocalizes to the cytoplasm. This relocalization is triggered by the intercellular pulling force of the leading cell and depends on the actomyosin-based cell contractility. Then in migrating cells, taking its cue from the intercellular pulling forces, which show long-distance ordering, merlin coordinates polarized Rac1 activation and lamellipodium formation on the multicellular length scale. Together, these results provide a distinct molecular mechanism linking intercellular forces to collective cell movements in migrating epithelia.