Tao and Rap2l ensure proper Misshapen activation and levels during Drosophila border cell migration

Collective cell migration is fundamental in development, wound healing, and metastasis. During Drosophila oogenesis, border cells (BCs) migrate collectively inside the egg chamber, controlled by the Ste20-like kinase Misshapen (Msn). Msn coordinates the restriction of protrusion formation and contractile forces within the cluster. Here, we demonstrate that Tao acts as an upstream activator of Msn in BCs. Depleting Tao significantly impedes BC migration, producing a phenotype similar to Msn loss of function. Furthermore, we show that the localization of Msn relies on its citron homology (CNH) domain, which interacts with the small GTPase Rap2l. Rap2l promotes the trafficking of Msn to the endolysosomal pathway. Depleting Rap2l elevates Msn levels by reducing its trafficking into late endosomes and increases overall contractility. These data suggest that Tao promotes Msn activation, while global Msn protein levels are controlled via Rap2l and the endolysosomal degradation pathway. Thus, two mechanisms ensure appropriate Msn levels and activation in BCs. [Display omitted] •Tao and Rap2l are required for the migration of Drosophila border cells (BCs)•Tao phosphorylation of Misshapen T194 promotes Misshapen activation in BCs•Msn localization at the membrane requires its CNH domain•Rap2l targets Misshapen to the endolysosomal pathway to control Misshapen levels Roberto et al. demonstrate that Misshapen is activated by the kinase Tao, while Rap2l promotes Misshapen trafficking to the endolysosomal pathway, controlling its global protein levels. Furthermore, they show that depletion of Tao or Rap2l impairs border cell migration.