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The GEF Trio controls endothelial cell size and arterial remodeling downstream of Vegf signaling in both zebrafish and cell models

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Item Type:Article
Title:The GEF Trio controls endothelial cell size and arterial remodeling downstream of Vegf signaling in both zebrafish and cell models
Creators Name:Klems, A. and van Rijssel, J. and Ramms, A.S. and Wild, R. and Hammer, J. and Merkel, M. and Derenbach, L. and Préau, L. and Hinkel, R. and Suarez-Martinez, I. and Schulte-Merker, S. and Vidal, R. and Sauer, S. and Kivelä, R. and Alitalo, K. and Kupatt, C. and van Buul, J.D. and le Noble, F.
Abstract:Arterial networks enlarge in response to increase in tissue metabolism to facilitate flow and nutrient delivery. Typically, the transition of a growing artery with a small diameter into a large caliber artery with a sizeable diameter occurs upon the blood flow driven change in number and shape of endothelial cells lining the arterial lumen. Here, using zebrafish embryos and endothelial cell models, we describe an alternative, flow independent model, involving enlargement of arterial endothelial cells, which results in the formation of large diameter arteries. Endothelial enlargement requires the GEF1 domain of the guanine nucleotide exchange factor Trio and activation of Rho-GTPases Rac1 and RhoG in the cell periphery, inducing F-actin cytoskeleton remodeling, myosin based tension at junction regions and focal adhesions. Activation of Trio in developing arteries in vivo involves precise titration of the Vegf signaling strength in the arterial wall, which is controlled by the soluble Vegf receptor Flt1.
Keywords:Cardiovascular Models, Cell Size, Cultured Cells, Endothelial Cells, Genetically Modified Animals, Guanine Nucleotide Exchange Factors, Human Umbilical Vein Endothelial Cells, Placenta Growth Factor, Protein-Serine-Threonine Kinases, rac1 GTP-Binding Protein, Signal Transduction, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-1, Vascular Remodeling, Zebrafish Proteins, Animals, Zebrafish
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:5319
Date:21 October 2020
Official Publication:https://doi.org/10.1038/s41467-020-19008-0
PubMed:View item in PubMed

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