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

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Klems , A , van Rijssel , J , Ramms , A S , Wild , R , Hammer , J , Merkel , M , Derenbach , L , Preau , L , Hinkel , R , Suarez-Martinez , I , Schulte-Merker , S , Vidal , R , Sauer , S , Kivelae , R , Alitalo , K , Kupatt , C , van Buul , J D & le Noble , F 2020 , ' The GEF Trio controls endothelial cell size and arterial remodeling downstream of Vegf signaling in both zebrafish and cell models ' , Nature Communications , vol. 11 , no. 1 , 5319 . https://doi.org/10.1038/s41467-020-19008-0

Title: The GEF Trio controls endothelial cell size and arterial remodeling downstream of Vegf signaling in both zebrafish and cell models
Author: Klems, Alina; van Rijssel, Jos; Ramms, Anne S.; Wild, Raphael; Hammer, Julia; Merkel, Melanie; Derenbach, Laura; Preau, Laetitia; Hinkel, Rabea; Suarez-Martinez, Irina; Schulte-Merker, Stefan; Vidal, Ramon; Sauer, Sascha; Kivelae, Riikka; Alitalo, Kari; Kupatt, Christian; van Buul, Jaap D.; le Noble, Ferdinand
Contributor: University of Helsinki, HUSLAB
Date: 2020-10-21
Language: eng
Number of pages: 20
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/321954
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. Arterial flow regulates artery diameter but other mechanisms may also affect this. Here, the authors show that the guanine nucleotide exchange factor Trio and GTPases Rac1 and RhoG, triggers F-actin remodeling in arterial endothelial cells, independent of flow, to enhance lumen diameter in zebrafish and cell models.
Subject: GROWTH-FACTOR
COLLATERAL CIRCULATION
ANGIOGENESIS
CADHERIN
ARTERIOGENESIS
MIGRATION
JUNCTIONS
ALK1
MECHANOTRANSDUCTION
SPECIFICATION
3111 Biomedicine
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