Epithelial Biology Laboratory, Cancer Research UK, London Research Institute, London WC2A 3LY, England, UK.
J Cell Biol. 2013 Jun 10;201(6):875-85. doi: 10.1083/jcb.201210073. Epub 2013 Jun 3.
Collective migration of Drosophila border cells depends on a dynamic actin cytoskeleton that is highly polarized such that it concentrates around the outer rim of the migrating cluster of cells. How the actin cytoskeleton becomes polarized in these cells to enable collective movement remains unknown. Here we show that the Hippo signaling pathway links determinants of cell polarity to polarization of the actin cytoskeleton in border cells. Upstream Hippo pathway components localize to contacts between border cells inside the cluster and signal through the Hippo and Warts kinases to polarize actin and promote border cell migration. Phosphorylation of the transcriptional coactivator Yorkie (Yki)/YAP by Warts does not mediate the function of this pathway in promoting border cell migration, but rather provides negative feedback to limit the speed of migration. Instead, Warts phosphorylates and inhibits the actin regulator Ena to activate F-actin Capping protein activity on inner membranes and thereby restricts F-actin polymerization mainly to the outer rim of the migrating cluster.
果蝇边缘细胞的集体迁移依赖于一个动态的肌动蛋白细胞骨架，该骨架高度极化，使其集中在迁移细胞簇的外边缘。肌动蛋白细胞骨架在这些细胞中如何极化以实现集体运动仍然未知。在这里，我们表明 Hippo 信号通路将细胞极性决定因素与边缘细胞中肌动蛋白细胞骨架的极化联系起来。上游 Hippo 通路成分定位于细胞簇内边缘细胞之间的接触处，并通过 Hippo 和 Warts 激酶发出信号，使肌动蛋白极化并促进边缘细胞迁移。Warts 对转录共激活因子 Yorkie (Yki)/YAP 的磷酸化并不介导该途径在促进边缘细胞迁移中的功能，而是提供负反馈以限制迁移速度。相反，Warts 磷酸化并抑制肌动蛋白调节剂 Ena，以激活内膜上的 F-肌动蛋白加帽蛋白活性，从而将 F-肌动蛋白聚合主要限制在迁移细胞簇的外边缘。
