title: Rab7a regulates cell migration through Rac1 and vimentin.
abstract: Rab7a, a small GTPase of the Rab family, is localized to late endosomes and controls late endocytic trafficking. The discovery of several Rab7a interacting proteins revealed that Rab7a function is closely connected to cytoskeletal elements. Indeed, Rab7a recruits on vesicles RILP and FYCO that are responsible for the movement of Rab7a-positive vesicles and/or organelles on microtubule tracks, but also directly interacts with Rac1, a fundamental regulator of actin cytoskeleton, and with peripherin and vimentin, two intermediate filament proteins. Considering all these interactions and, in particular, the fact that Rac1 and vimentin are key factors for cellular motility, we investigated a possible role of Rab7a in cell migration. We show here that Rab7a is needed for cell migration as Rab7a depletion causes slower migration of NCI H1299 cells affecting cell velocity and directness. Rab7a depletion negatively affects adhesion and spreading onto fibronectin substrates, altering β1-integrin activation, localization and intracellular trafficking, and myosin X localization. In fact, Rab7a-depleted cells show 40% less filopodia and active integrin accumulates at the leading edge of migrating cells. Furthermore, Rab7a depletion decreases the amount of active Rac1 but not its abundance and reduces the number of cells with vimentin filaments facing the wound, indicating that Rab7a has a role in the orientation of vimentin filaments during migration. In conclusion, our results demonstrate a key role of Rab7a in the regulation of different aspects of cell migration.
authors.affiliation: Department of Biological and Environmental Sciences and Technologies, (DiSTeBA) University of Salento, Via Provinciale Monteroni 165, 73100 Lecce, Italy; Department of Biosciences, Centre for Immune Regulation, University of Oslo, Blindernveien 31, 0371 Oslo, Norway.
authors.forename: Azzurra
authors.initials: A
authors.lastname: Margiotta
authors.affiliation: Department of Biosciences, Centre for Immune Regulation, University of Oslo, Blindernveien 31, 0371 Oslo, Norway. Electronic address: c.a.m.progida@ibv.uio.no.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Progida
authors.affiliation: Department of Biosciences, Centre for Immune Regulation, University of Oslo, Blindernveien 31, 0371 Oslo, Norway. Electronic address: oddmund.bakke@ibv.uio.no.
authors.forename: Oddmund
authors.initials: O
authors.lastname: Bakke
authors.affiliation: Department of Biological and Environmental Sciences and Technologies, (DiSTeBA) University of Salento, Via Provinciale Monteroni 165, 73100 Lecce, Italy. Electronic address: cecilia.bucci@unisalento.it.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bucci
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D014746:Vimentin / Q000502:physiology*; D014945:Wound Healing; D020691:rab GTP-Binding Proteins / Q000502:physiology*; D000090802:rab7 GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein / Q000502:physiology*
chemical_list: C107953:RAC1 protein, human; D014746:Vimentin; D000090802:rab7 GTP-Binding Proteins; D020691:rab GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein
keywords: Cell migration; Myosin X; Rab7a; Rac1; Vimentin; β1-integrin