RhoB controls endothelial barrier recovery by inhibiting Rac1 trafficking to the cell border

DOI PDF 被引用文献3件
  • Beatriz Marcos-Ramiro
    Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, 28049 Madrid, Spain 1
  • Diego García-Weber
    Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, 28049 Madrid, Spain 1
  • Susana Barroso
    Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, 28049 Madrid, Spain 1
  • Jorge Feito
    Servicio de Anatomía Patológica, Hospital Universitario de Salamanca, 37007 Salamanca, Spain 2
  • María C. Ortega
    Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, 28049 Madrid, Spain 1
  • Eva Cernuda-Morollón
    Neurology Department, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain 3
  • Natalia Reglero-Real
    Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, 28049 Madrid, Spain 1
  • Laura Fernández-Martín
    Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, 28049 Madrid, Spain 1
  • Maria C. Durán
    Biomedicine, Biotechnology and Public Health Department, University of Cadiz, 11519 Cadiz, Spain 4
  • Miguel A. Alonso
    Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, 28049 Madrid, Spain 1
  • Isabel Correas
    Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, 28049 Madrid, Spain 1
  • Susan Cox
    Randall Division of Cell and Molecular Biophysics, King’s College London, SE1 1UL London, England, UK 5
  • Anne J. Ridley
    Randall Division of Cell and Molecular Biophysics, King’s College London, SE1 1UL London, England, UK 5
  • Jaime Millán
    Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Universidad Autónoma de Madrid, 28049 Madrid, Spain 1

説明

<jats:p>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.</jats:p>

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