Toret, C.P., Shivakumar, P.C., Lenne, P.F., Le Bivic, A. (2018). The ELMO-MBC complex and RhoGAP19D couple Rho family GTPases during mesenchymal-to-epithelial-like transitions.  Development 145(4): dev157495.

FBrf0241534

Research paper

Many metazoan developmental processes require cells to transition between migratory mesenchymal- and adherent epithelial-like states. These transitions require Rho GTPase-mediated actin rearrangements downstream of integrin and cadherin pathways. A regulatory toolbox of GEF and GAP proteins precisely coordinates Rho protein activities, yet defining the involvement of specific regulators within a cellular context remains a challenge due to overlapping and coupled activities. Here we demonstrate that Drosophila dorsal closure is a powerful model for Rho GTPase regulation during transitions from leading edges to cadherin contacts. During these transitions a Rac GEF elmo-mbc complex regulates both lamellipodia and Rho1-dependent, actomyosin-mediated tension at initial cadherin contacts. Moreover, the Rho GAP Rhogap19d controls Rac and Rho GTPases during the same processes and genetically regulates the elmo-mbc complex. This study presents a fresh framework to understand the inter-relationship between GEF and GAP proteins that tether Rac and Rho cycles during developmental processes.