RhoB controls endothelial barrier recovery by inhibiting Rac1 trafficking to the cell border
Publisher
Rockefeller University PressDate
2016-05-02Citation
10.1083/jcb.201504038
Journal of Cell Biology 213.3 (2016): 385–402
ISSN
0021-9525 (print); 1540-8140 (online)DOI
10.1083/jcb.201504038Funded by
This work supported by Ministerio de Economía y Competitividad grants SAF2014-57950-R (to J. Millán), BFU2015–67266-R (to M.A. Alonso), and BFU2011-22859 (to I. Correas); Comunidad Madrid grant S2010/ BMD-2305; and Cancer Research UK (A.J. Ridley). M.C. Ortega and S. Barroso are supported by Endocornea, convenio colaboración Consejo Superior de Investigaciones Científicas, from Instituto Investigaciones Sanitarias Fundación Jiménez Díaz. B. Marcos-Ramiro and D. GarcíaWeber are recipients of a Foreign Policy Initiative fellowship from Ministerio de Economía y CompetitividadProject
Comunidad de Madrid. S2010/ BMD-2305Editor's Version
https://doi.org/10.1083/jcb.201504038Subjects
Membrane and lipid biology; Trafficking; Biología y Biomedicina / BiologíaRights
© 2016 Marcos-Ramiro et alEsta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-CompartirIgual 4.0 Internacional.
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
Files in this item
Google Scholar:Marcos-Ramiro, Beatriz
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García-Weber, Diego
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Barroso, Susana
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Feito, Jorge
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Ortega, María C.
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Cernuda-Morollón, Eva
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Reglero Real, Natalia
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Fernández-Martín, Laura
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Durán, Maria C.
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Alonso, Miguel A.
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Correas Hornero, María Isabel
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Cox, Susan
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Ridley, Anne J.
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Millán, Jaime
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