Pak3 regulates apical-basal polarity in migrating border cells during Drosophila oogenesis
Pak3 regulates apical-basal polarity in migrating border cells during Drosophila oogenesis
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DOI：
10.1242/dev.125682
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发表时间：
2015-11-01
期刊：
影响因子：
4.6
通讯作者：
Prasad, Mohit
中科院分区：
文献类型：
--
作者：
Felix, Martina;Chayengia, Mrinal;Prasad, Mohit
群体细胞迁移是一个高度协调的过程，涉及许多生理事件，例如形态发生、伤口愈合和肿瘤转移。与单个细胞不同，集体移动的细胞在物理上彼此附着，并在迁移阶段保留一定程度的顶端-基底极性。尽管人们对方向感知了解很多，但多细胞运动中极性如何调节仍不清楚。在这里，我们报告了蛋白激酶 Pak3 在果蝇卵子发生过程中迁移边界细胞簇中维持顶端-基底极性中的作用。 Pak3 在边缘细胞中富集，其功能的下调会阻碍边缘细胞的运动。延时成像表明 Pak3 影响边缘细胞簇的突出行为，特别是调节突出的稳定性和方向性。 Pak3 在引导受体信号下游发挥作用，调节迁移边缘细胞中 F-肌动蛋白的水平和分布。我们还提供了证据，证明 Pak3 与横向极性标记 Scribble 存在遗传相互作用，并且它调节移动边缘细胞中的 JNK 信号传导。由于 Pak3 耗尽会导致几个顶端-基底极性标记的错误定位，而 Jra 的过度表达可以挽救 Pak3 耗尽簇的极性，因此我们建议 Pak3 通过 JNK 信号传导发挥作用，调节迁移边界细胞簇的顶端-基底极性。我们还观察到 Rac1 耗尽的边界细胞簇中顶端-基底极性的丧失，表明引导受体信号传导通过 Rac GTPase 和 Pak3 发挥作用，调节簇的整体极性并介导边界细胞向卵母细胞边界的有效集体运动。
Group cell migration is a highly coordinated process that is involved in a number of physiological events such as morphogenesis, wound healing and tumor metastasis. Unlike single cells, collectively moving cells are physically attached to each other and retain some degree of apical-basal polarity during the migratory phase. Although much is known about direction sensing, how polarity is regulated in multicellular movement remains unclear. Here we report the role of the protein kinase Pak3 in maintaining apical-basal polarity in migrating border cell clusters during Drosophila oogenesis. Pak3 is enriched in border cells and downregulation of its function impedes border cell movement. Time-lapse imaging suggests that Pak3 affects protrusive behavior of the border cell cluster, specifically regulating the stability and directionality of protrusions. Pak3 functions downstream of guidance receptor signaling to regulate the level and distribution of F-actin in migrating border cells. We also provide evidence that Pak3 genetically interacts with the lateral polarity marker Scribble and that it regulates JNK signaling in the moving border cells. Since Pak3 depletion results in mislocalization of several apical-basal polarity markers and overexpression of Jra rescues the polarity of the Pak3-depleted cluster, we propose that Pak3 functions through JNK signaling to modulate apical-basal polarity of the migrating border cell cluster. We also observe loss of apical-basal polarity in Rac1-depleted border cell clusters, suggesting that guidance receptor signaling functions through Rac GTPase and Pak3 to regulate the overall polarity of the cluster and mediate efficient collective movement of the border cells to the oocyte boundary.