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

Autor:	Klems A; Department of Cell and Developmental Biology, Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT), Fritz Haber Weg 4, 76131, Karlsruhe, Germany., van Rijssel J; Molecular Cell Biology lab, Department Molecular and Cellular Hemostasis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center at the University of Amsterdam, Plesmanlaan 125, 1066CX, Amsterdam, The Netherlands., Ramms AS; Department of Cell and Developmental Biology, Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT), Fritz Haber Weg 4, 76131, Karlsruhe, Germany.; Institute for Biological and Chemical Systems-Biological Information Processing, Karlsruhe Institute of Technology (KIT), PO Box 3640, 76021, Karlsruhe, Germany., Wild R; Department of Cell and Developmental Biology, Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT), Fritz Haber Weg 4, 76131, Karlsruhe, Germany., Hammer J; Department of Cell and Developmental Biology, Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT), Fritz Haber Weg 4, 76131, Karlsruhe, Germany., Merkel M; Department of Cell and Developmental Biology, Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT), Fritz Haber Weg 4, 76131, Karlsruhe, Germany., Derenbach L; Department of Cell and Developmental Biology, Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT), Fritz Haber Weg 4, 76131, Karlsruhe, Germany., Préau L; Department of Cell and Developmental Biology, Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT), Fritz Haber Weg 4, 76131, Karlsruhe, Germany., Hinkel R; Laboratory Animal Science Unit, Leibnitz-Institut für Primatenforschung, Deutsches Primatenzentrum GmbH, Kellnerweg 4, 37077 Göttingen, Germany and DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany., Suarez-Martinez I; Institute of Cardiovascular Organogenesis and Regeneration WWU Münster, Münster, Germany & Faculty of Medicine, WWU Münster, Münster, Germany & Cells in Motion Cluster of Excellence, Münster, Münster, Germany., Schulte-Merker S; Institute of Cardiovascular Organogenesis and Regeneration WWU Münster, Münster, Germany & Faculty of Medicine, WWU Münster, Münster, Germany & Cells in Motion Cluster of Excellence, Münster, Münster, Germany., Vidal R; Max Delbrück Center for Molecular Medicine (MDC), Berlin Institute of Medical Systems Biology & Berlin Institute of Health, Robert Rössle Strasse 10, 13092, Berlin, Germany., Sauer S; Max Delbrück Center for Molecular Medicine (MDC), Berlin Institute of Medical Systems Biology & Berlin Institute of Health, Robert Rössle Strasse 10, 13092, Berlin, Germany., Kivelä R; Stem Cells and Metabolism Research Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, and Wihuri Research Institute, Helsinki, Finland., Alitalo K; Translational Cancer Medicine Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, and Wihuri Research Institute, Helsinki, Finland., Kupatt C; Klinik und Poliklinik für Innere Medizin I, Klinikum rechts der Isar, TUM Munich, Germany, and DZHK, (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany., van Buul JD; Molecular Cell Biology lab, Department Molecular and Cellular Hemostasis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center at the University of Amsterdam, Plesmanlaan 125, 1066CX, Amsterdam, The Netherlands.; Leeuwenhoek Centre for Advanced Microscopy, section Molecular Cytology at Swammerdam Institute for Life Sciences at University of Amsterdam, Amsterdam, The Netherlands., le Noble F; Department of Cell and Developmental Biology, Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT), Fritz Haber Weg 4, 76131, Karlsruhe, Germany. ferdinand.noble@kit.edu.; Institute for Biological and Chemical Systems-Biological Information Processing, Karlsruhe Institute of Technology (KIT), PO Box 3640, 76021, Karlsruhe, Germany. ferdinand.noble@kit.edu.; Institute of Experimental Cardiology, University of Heidelberg, Heidelberg Germany and DZHK (German Center for Cardiovascular Research), partner site Heidelberg/Mannheim, Heidelberg, Germany. ferdinand.noble@kit.edu.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2020 Oct 21; Vol. 11 (1), pp. 5319. Date of Electronic Publication: 2020 Oct 21.
DOI:	10.1038/s41467-020-19008-0
Abstrakt:	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.
Databáze:	MEDLINE
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