Spatial regulation of Dia and Myosin-II by RhoGEF2 controls initiation of E-cadherin endocytosis during epithelial morphogenesis
Spatial regulation of Dia and Myosin-II by RhoGEF2 controls initiation of E-cadherin endocytosis during epithelial morphogenesis
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DOI：
10.1038/ncb2224
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发表时间：
2011-05-11
影响因子：
21.3
通讯作者：
Lecuit, Thomas
中科院分区：
文献类型：
--
作者：
Levayer, Romain;Pelissier-Monier, Anne;Lecuit, Thomas
e -钙粘蛋白在上皮细胞形态发生中起关键作用。它控制组织内聚所需的细胞间粘附，并锚定肌动球蛋白驱动的张力，以改变细胞形状。在早期果蝇胚胎中，Myosin-II （Myo-II）控制着细胞连接和组织扩展的平面极化重构。e -钙粘蛋白的分布也是平面极化的，与肌凝蛋白ii的分布互补。在这里，我们发现e -钙粘蛋白极性是由网格蛋白和动力蛋白介导的内吞作用的极化调节控制的。阻断e -钙粘蛋白内吞导致细胞嵌入缺陷。我们描述了一条通过调节AP2和E-cadherin募集网格蛋白外壳来控制E-cadherin内吞作用启动的途径。这需要双胍透明蛋白（Dia）和肌球蛋白ii的协同作用。它们的活性受鸟嘌呤交换因子RhoGEF2控制，RhoGEF2是平面极化的，在非插层区不存在。最后，我们提供的证据表明，Dia和Myo-II通过调节E-cadherin的横向聚集来控制E-cadherin内吞作用的启动。
E-cadherin plays a pivotal role in epithelial morphogenesis. It controls the intercellular adhesion required for tissue cohesion and anchors the actomyosin-driven tension needed to change cell shape. In the early Drosophila embryo, Myosin-II (Myo-II) controls the planar polarized remodelling of cell junctions and tissue extension. The E-cadherin distribution is also planar polarized and complementary to the Myosin-II distribution. Here we show that E-cadherin polarity is controlled by the polarized regulation of clathrin- and dynamin-mediated endocytosis. Blocking E-cadherin endocytosis resulted in cell intercalation defects. We delineate a pathway that controls the initiation of E-cadherin endocytosis through the regulation of AP2 and clathrin coat recruitment by E-cadherin. This requires the concerted action of the formin Diaphanous (Dia) and Myosin-II. Their activity is controlled by the guanine exchange factor RhoGEF2, which is planar polarized and absent in non-intercalating regions. Finally, we provide evidence that Dia and Myo-II control the initiation of E-cadherin endocytosis by regulating the lateral clustering of E-cadherin.