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EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity

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EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity. / Frye, Maike; Stritt, Simon; Ortsäter, Henrik; Hernandez Vasquez, Magda; Kaakinen, Mika; Vicente, Andres; Wiseman, John; Eklund, Lauri; Martínez-Torrecuadrada, Jorge L; Vestweber, Dietmar; Mäkinen, Taija.

In: ELIFE, Vol. 9, 08.09.2020.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Frye, M, Stritt, S, Ortsäter, H, Hernandez Vasquez, M, Kaakinen, M, Vicente, A, Wiseman, J, Eklund, L, Martínez-Torrecuadrada, JL, Vestweber, D & Mäkinen, T 2020, 'EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity', ELIFE, vol. 9. https://doi.org/10.7554/eLife.57732

APA

Frye, M., Stritt, S., Ortsäter, H., Hernandez Vasquez, M., Kaakinen, M., Vicente, A., Wiseman, J., Eklund, L., Martínez-Torrecuadrada, J. L., Vestweber, D., & Mäkinen, T. (2020). EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity. ELIFE, 9. https://doi.org/10.7554/eLife.57732

Vancouver

Frye M, Stritt S, Ortsäter H, Hernandez Vasquez M, Kaakinen M, Vicente A et al. EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity. ELIFE. 2020 Sep 8;9. https://doi.org/10.7554/eLife.57732

Bibtex

@article{ca7dc5030d204f209c4870009b22e2e8,
title = "EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity",
abstract = "Endothelial integrity is vital for homeostasis and adjusted to tissue demands. Although fluid uptake by lymphatic capillaries is a critical attribute of the lymphatic vasculature, the barrier function of collecting lymphatic vessels is also important by ensuring efficient fluid drainage as well as lymph node delivery of antigens and immune cells. Here, we identified the transmembrane ligand EphrinB2 and its receptor EphB4 as critical homeostatic regulators of collecting lymphatic vessel integrity. Conditional gene deletion in mice revealed that EphrinB2/EphB4 signalling is dispensable for blood endothelial barrier function, but required for stabilization of lymphatic endothelial cell (LEC) junctions in different organs of juvenile and adult mice. Studies in primary human LECs further showed that basal EphrinB2/EphB4 signalling controls junctional localisation of the tight junction protein CLDN5 and junction stability via Rac1/Rho-mediated regulation of cytoskeletal contractility. EphrinB2/EphB4 signalling therefore provides a potential therapeutic target to selectively modulate lymphatic vessel permeability and function.",
author = "Maike Frye and Simon Stritt and Henrik Orts{\"a}ter and {Hernandez Vasquez}, Magda and Mika Kaakinen and Andres Vicente and John Wiseman and Lauri Eklund and Mart{\'i}nez-Torrecuadrada, {Jorge L} and Dietmar Vestweber and Taija M{\"a}kinen",
note = "{\textcopyright} 2020, Frye et al.",
year = "2020",
month = sep,
day = "8",
doi = "10.7554/eLife.57732",
language = "English",
volume = "9",
journal = "ELIFE",
issn = "2050-084X",
publisher = "eLife Sciences Publications",

}

RIS

TY - JOUR

T1 - EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity

AU - Frye, Maike

AU - Stritt, Simon

AU - Ortsäter, Henrik

AU - Hernandez Vasquez, Magda

AU - Kaakinen, Mika

AU - Vicente, Andres

AU - Wiseman, John

AU - Eklund, Lauri

AU - Martínez-Torrecuadrada, Jorge L

AU - Vestweber, Dietmar

AU - Mäkinen, Taija

N1 - © 2020, Frye et al.

PY - 2020/9/8

Y1 - 2020/9/8

N2 - Endothelial integrity is vital for homeostasis and adjusted to tissue demands. Although fluid uptake by lymphatic capillaries is a critical attribute of the lymphatic vasculature, the barrier function of collecting lymphatic vessels is also important by ensuring efficient fluid drainage as well as lymph node delivery of antigens and immune cells. Here, we identified the transmembrane ligand EphrinB2 and its receptor EphB4 as critical homeostatic regulators of collecting lymphatic vessel integrity. Conditional gene deletion in mice revealed that EphrinB2/EphB4 signalling is dispensable for blood endothelial barrier function, but required for stabilization of lymphatic endothelial cell (LEC) junctions in different organs of juvenile and adult mice. Studies in primary human LECs further showed that basal EphrinB2/EphB4 signalling controls junctional localisation of the tight junction protein CLDN5 and junction stability via Rac1/Rho-mediated regulation of cytoskeletal contractility. EphrinB2/EphB4 signalling therefore provides a potential therapeutic target to selectively modulate lymphatic vessel permeability and function.

AB - Endothelial integrity is vital for homeostasis and adjusted to tissue demands. Although fluid uptake by lymphatic capillaries is a critical attribute of the lymphatic vasculature, the barrier function of collecting lymphatic vessels is also important by ensuring efficient fluid drainage as well as lymph node delivery of antigens and immune cells. Here, we identified the transmembrane ligand EphrinB2 and its receptor EphB4 as critical homeostatic regulators of collecting lymphatic vessel integrity. Conditional gene deletion in mice revealed that EphrinB2/EphB4 signalling is dispensable for blood endothelial barrier function, but required for stabilization of lymphatic endothelial cell (LEC) junctions in different organs of juvenile and adult mice. Studies in primary human LECs further showed that basal EphrinB2/EphB4 signalling controls junctional localisation of the tight junction protein CLDN5 and junction stability via Rac1/Rho-mediated regulation of cytoskeletal contractility. EphrinB2/EphB4 signalling therefore provides a potential therapeutic target to selectively modulate lymphatic vessel permeability and function.

U2 - 10.7554/eLife.57732

DO - 10.7554/eLife.57732

M3 - SCORING: Journal article

C2 - 32897857

VL - 9

JO - ELIFE

JF - ELIFE

SN - 2050-084X

ER -