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

doi:10.1083/jcb.201504038

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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 language	English
Pages (from-to)	385-402
Number of pages	18
Journal	The Journal of cell biology
Volume	213
Issue number	3
Early online date	2 May 2016
DOIs	https://doi.org/10.1083/jcb.201504038
Publication status	Published - 2 May 2016

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RhoB controls endothelial_COX_Accepted 13Apr2016_GREEN VoRFinal published version, 4.95 MBLicence: CC BY-NC-SA

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Marcos-Ramiro, B., García-Weber, D., Barroso, S., Feito, J., Ortega, M. C., Cernuda-Morollón, E., Reglero-Real, N., Fernández-Martín, L., Durán, M. C., Alonso, M. A., Correas, I., Cox, S., Ridley, A. J., & Millán, J. (2016). RhoB controls endothelial barrier recovery by inhibiting Rac1 trafficking to the cell border. The Journal of cell biology, 213(3), 385-402. https://doi.org/10.1083/jcb.201504038

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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.",

author = "Beatriz Marcos-Ramiro and Diego Garc{\'i}a-Weber and Susana Barroso and Jorge Feito and Ortega, {Mar{\'i}a C.} and Eva Cernuda-Moroll{\'o}n and Natalia Reglero-Real and Laura Fern{\'a}ndez-Mart{\'i}n and Dur{\'a}n, {Maria C.} and Alonso, {Miguel A.} and Isabel Correas and Susan Cox and Ridley, {Anne J.} and Jaime Mill{\'a}n",

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Marcos-Ramiro, B, García-Weber, D, Barroso, S, Feito, J, Ortega, MC, Cernuda-Morollón, E, Reglero-Real, N, Fernández-Martín, L, Durán, MC, Alonso, MA, Correas, I, Cox, S , Ridley, AJ & Millán, J 2016, 'RhoB controls endothelial barrier recovery by inhibiting Rac1 trafficking to the cell border', The Journal of cell biology, vol. 213, no. 3, pp. 385-402. https://doi.org/10.1083/jcb.201504038

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T1 - RhoB controls endothelial barrier recovery by inhibiting Rac1 trafficking to the cell border

AU - Marcos-Ramiro, Beatriz

AU - García-Weber, Diego

AU - Barroso, Susana

AU - Feito, Jorge

AU - Ortega, María C.

AU - Cernuda-Morollón, Eva

AU - Reglero-Real, Natalia

AU - Fernández-Martín, Laura

AU - Durán, Maria C.

AU - Alonso, Miguel A.

AU - Correas, Isabel

AU - Cox, Susan

AU - Ridley, Anne J.

AU - Millán, Jaime

PY - 2016/5/2

Y1 - 2016/5/2

N2 - 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.

AB - 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.

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JO - The Journal of cell biology

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ER -

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

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