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oai:repisalud.isciii.es:20.500.12105/272592026-02-23T01:17:34Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Bravo-Cordero, José J author Cordani, Marco author Soriano, Silvia F author Díez, Begoña author Muñoz-Agudo, Carmen author Casanova-Acebes, Maria author Boullosa, César author Guadamillas, Marta C author Ezkurdia, Iakes author González-Pisano, David author Del Pozo, Miguel A author Montoya, María C author 2016-04-15 Rab8 is a small Ras-related GTPase that regulates polarized membrane transport to the plasma membrane. Here, we developed a high-content analysis (HCA) tool to dissect Rab8-mediated actin and focal adhesion reorganization that revealed that Rab8 activation significantly induced Rac1 and Tiam1 to mediate cortical actin polymerization and RhoA-dependent stress fibre disassembly. Rab8 activation increased Rac1 activity, whereas its depletion activated RhoA, which led to reorganization of the actin cytoskeleton. Rab8 was also associated with focal adhesions, promoting their disassembly in a microtubule-dependent manner. This Rab8 effect involved calpain, MT1-MMP (also known as MMP14) and Rho GTPases. Moreover, we demonstrate the role of Rab8 in the cell migration process. Indeed, Rab8 is required for EGF-induced cell polarization and chemotaxis, as well as for the directional persistency of intrinsic cell motility. These data reveal that Rab8 drives cell motility by mechanisms both dependent and independent of Rho GTPases, thereby regulating the establishment of cell polarity, turnover of focal adhesions and actin cytoskeleton rearrangements, thus determining the directionality of cell migration. J Cell Sci . 2016 Apr 15;129(8):1734-49. Journal of Cell Science 26940916 https://hdl.handle.net/20.500.12105/27259 Actin Cytoskeleton Focal adhesion Migration Proteases Rab8 Rho GTPases A novel high-content analysis tool reveals Rab8-driven cytoskeletal reorganization through Rho GTPases, calpain and MT1-MMP.