The ELMO-MBC complex and RhoGAP19D couple Rho family GTPases during mesenchymal-to-epithelial-like transitions [RESEARCH ARTICLE]

Christopher P. Toret, Pruthvi C. Shivakumar, Pierre-Francois Lenne, and Andre Le Bivic

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 with which to understand the inter-relationship between GEF and GAP proteins that tether Rac and Rho cycles during developmental processes.

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