title: RhoB controls endothelial barrier recovery by inhibiting Rac1 trafficking to the cell border.
abstract: Endothelial barrier dysfunction underlies chronic inflammatory diseases. In searching for new proteins essential to the human endothelial inflammatory response, we have found that the endosomal GTPase RhoB is up-regulated in response to inflammatory cytokines and expressed in the endothelium of some chronically inflamed tissues. We show that although RhoB and the related RhoA and RhoC play additive and redundant roles in various aspects of endothelial barrier function, RhoB specifically inhibits barrier restoration after acute cell contraction by preventing plasma membrane extension. During barrier restoration, RhoB trafficking is induced between vesicles containing RhoB nanoclusters and plasma membrane protrusions. The Rho GTPase Rac1 controls membrane spreading and stabilizes endothelial barriers. We show that RhoB colocalizes with Rac1 in endosomes and inhibits Rac1 activity and trafficking to the cell border during barrier recovery. Inhibition of endosomal trafficking impairs barrier reformation, whereas induction of Rac1 translocation to the plasma membrane accelerates it. Therefore, RhoB-specific regulation of Rac1 trafficking controls endothelial barrier integrity during inflammation.
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Marcos-Ramiro
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: García-Weber
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Barroso
authors.affiliation: Servicio de Anatomía Patológica, Hospital Universitario de Salamanca, 37007 Salamanca, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Feito
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: María C
authors.initials: MC
authors.lastname: Ortega
authors.affiliation: Neurology Department, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Cernuda-Morollón
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Reglero-Real
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Fernández-Martín
authors.affiliation: Biomedicine, Biotechnology and Public Health Department, University of Cadiz, 11519 Cadiz, Spain.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Durán
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Alonso
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Correas
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, SE1 1UL London, England, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Cox
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, SE1 1UL London, England, UK.
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Ridley
authors.affiliation: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, 28049 Madrid, Spain jmillan@cbm.csic.es.
authors.forename: Jaime
authors.initials: J
authors.lastname: Millán
mesh_terms: D042783:Endothelial Cells / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000145:classification; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D021381:Protein Transport; D048069:Tumor Necrosis Factors / Q000494:pharmacology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D020743:rhoB GTP-Binding Protein / Q000378:metabolism / Q000502:physiology*
chemical_list: D048069:Tumor Necrosis Factors; D020830:rac1 GTP-Binding Protein; D020743:rhoB GTP-Binding Protein