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

Beatriz Marcos-Ramiro, Diego García-Weber, Susana Barroso, Jorge Feito, María C Ortega, Eva Cernuda-Morollón, Natalia Reglero-Real, Laura Fernández-Martín, Maria C Durán, Miguel A Alonso, Isabel Correas, Susan Cox, Anne J Ridley, Jaime Millán

Research output: Contribution to journalArticle (Academic Journal)

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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.

Original languageEnglish
Pages (from-to)385-402
Number of pages18
JournalJournal of Cell Biology
Volume213
Issue number3
Early online date2 May 2016
DOIs
Publication statusPublished - 9 May 2016

Keywords

  • Endothelial Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Immunohistochemistry
  • Intestines
  • Protein Transport
  • Tumor Necrosis Factors
  • rac1 GTP-Binding Protein
  • rhoB GTP-Binding Protein
  • Journal Article

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