RT Journal Article
T1 A novel high-content analysis tool reveals Rab8-driven cytoskeletal reorganization through Rho GTPases, calpain and MT1-MMP
A1 Bravo-Cordero, José
A1 Cordani, Marco
A1 Soriano, Silvia
A1 Díez, Begoña
A1 Muñoz-Agudo, Carmen
A1 Casanova-Acebes, María
A1 Boullosa, César
A1 Guadamillas, Marta
A1 Ezkurdia, Iakes
A1 González-Pisano, David
A1 Pozo, Miguel Angel del
A1 Montoya Redondo, María Luisa
AB 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.
PB The Company of Biologist
YR 2016
FD 2016
LK https://hdl.handle.net/20.500.14352/97219
UL https://hdl.handle.net/20.500.14352/97219
LA eng
NO Bravo-Cordero, José J., et al. «A Novel High-Content Analysis Tool Reveals Rab8-Driven Cytoskeletal Reorganization through Rho GTPases, Calpain and MT1-MMP». Journal of Cell Science, vol. 129, n.o 8, abril de 2016, pp. 1734-49.  https://doi.org/10.1242/jcs.174920.
DS Docta Complutense
RD 25 dic 2025