title: Activation of Rac1 by RhoG regulates cell migration.
abstract: Cell migration is essential for normal development and many pathological processes. Rho-family small GTPases play important roles in this event. In particular, Rac regulates lamellipodia formation at the leading edge during migration. The small GTPase RhoG activates Rac through its effector ELMO and the ELMO-binding protein Dock180, which functions as a Rac-specific guanine nucleotide exchange factor. Here we investigated the role of RhoG in cell migration. RNA interference-mediated knockdown of RhoG in HeLa cells reduced cell migration in Transwell and scratch-wound migration assays. In RhoG-knockdown cells, activation of Rac1 and formation of lamellipodia at the leading edge in response to wounding were attenuated. By contrast, expression of active RhoG promoted cell migration through ELMO and Dock180. However, the interaction of Dock180 with Crk was dispensable for the activation of Rac1 and promotion of cell migration by RhoG. Taken together, these results suggest that RhoG contributes to the regulation of Rac activity in migrating cells.
authors.affiliation: Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan. hirokato@pharm.kyoto-u.ac.jp
authors.forename: Hironori
authors.initials: H
authors.lastname: Katoh
authors.forename: Kiyo
authors.initials: K
authors.lastname: Hiramoto
authors.forename: Manabu
authors.initials: M
authors.lastname: Negishi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D050737:Proto-Oncogene Proteins c-crk / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C485285:CRK protein, human; C099818:DOCK1 protein, human; C465214:ELMO1 protein, human; D050737:Proto-Oncogene Proteins c-crk; D011993:Recombinant Fusion Proteins; C075397:RHOG protein, human; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins