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bioRxiv · 10.1101/244343

Coupling of Rho family GTPases during mesenchymal-to-epithelial-like transitions

Abstract

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 simple, powerful model for Rho GTPase regulation during leading edge to cadherin contact transitions. During these transitions a Rac GEF elmo-dock complex regulates both lamellipodia and Rho1-dependent, actomyosin-mediated tension at initial cadherin contacts. Moreover, the Drosophila Rho GAP arhgap21 ortholog controls Rac and Rho GTPases during the same processes and genetically regulates the elmo-dock 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.

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Toret, C., Shivakumar, P., Lenne, P.-F., LE BIVIC, A.. 2018-01-07. Coupling of Rho family GTPases during mesenchymal-to-epithelial-like transitions. https://doi.org/10.1101/244343

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