Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, QC, Canada.
Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, QC, Canada; Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.
Cell Rep. 2019 Sep 17;28(12):3238-3248.e3. doi: 10.1016/j.celrep.2019.08.044.
Collective cell migration is involved in various developmental and pathological processes, including the dissemination of various cancer cells. During Drosophila melanogaster oogenesis, a group of cells called border cells migrate collectively toward the oocyte. Herein, we show that members of the Arf family of small GTPases and some of their regulators are required for normal border cell migration. Notably, we found that the ArfGAP Drongo and its GTPase-activating function are essential for the initial detachment of the border cell cluster from the basal lamina. We demonstrate through protein localization and genetic interactions that Drongo controls the localization of the myosin phosphatase in order to regulate myosin II activity at the back of the cluster. Moreover, we show that toward the class III Arf, Drongo acts antagonistically to the guanine exchange factor Steppke. Overall, our work describes a mechanistic pathway that promotes the local actomyosin contractility necessary for border cell detachment.
细胞集体迁移参与了各种发育和病理过程，包括各种癌细胞的扩散。在果蝇的卵子发生过程中，一群被称为边缘细胞的细胞集体向卵母细胞迁移。在此，我们表明，小 GTPase 的 Arf 家族成员及其一些调节剂对于正常的边缘细胞迁移是必需的。值得注意的是，我们发现 ArfGAP Drongo 及其 GTPase 激活功能对于边缘细胞簇最初与基底膜分离是必需的。我们通过蛋白质定位和遗传相互作用证明，Drongo 控制肌球蛋白磷酸酶的定位，以调节簇后部的肌球蛋白 II 活性。此外，我们表明，针对 class III Arf，Drongo 与鸟嘌呤交换因子 Steppke 拮抗。总的来说，我们的工作描述了一种促进局部肌动球蛋白收缩所必需的机制途径，这种收缩对于边缘细胞的脱离是必需的。
