The ArfGAP Drongo Promotes Actomyosin Contractility during Collective Cell Migration by Releasing Myosin Phosphatase from the Trailing Edge

Abstract

Summary: 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. : Zeledon et al. identify the ArfGAP Drongo as a regulator of border cell migration in Drosophila. Drongo acts antagonistically to the ArfGEF Steppke on Arf51F. By keeping the activity of Arf51F low, Drongo prevents the recruitment of myosin phosphatase and ensures proper contractility at the back of border cell clusters. Keywords: collective cell migration, Arf GTPases, actomyosin contractility, Drosophila, border cell migration, myosin phosphatase