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

Animals Animals, Genetically Modified Cell Size Cells, Cultured Endothelial Cells / cytology Guanine Nucleotide Exchange Factors / genetics Human Umbilical Vein Endothelial Cells Humans Models, Cardiovascular Placenta Growth Factor / genetics Protein Serine-Threonine Kinases / genetics Signal Transduction Vascular Endothelial Growth Factor A / genetics Vascular Endothelial Growth Factor Receptor-1 / genetics Vascular Remodeling / genetics Zebrafish / embryology Zebrafish Proteins / genetics rac1 GTP-Binding Protein / genetics

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
21 10 2020
Historique:
received: 30 10 2019
accepted: 22 09 2020
entrez: 22 10 2020
pubmed: 23 10 2020
medline: 11 11 2020
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-020-19008-0 PMID: 33087700 PMC: PMC7578835
pubmed: 33087700
doi: 10.1038/s41467-020-19008-0
pii: 10.1038/s41467-020-19008-0
pmc: PMC7578835
doi:

Substances chimiques

Guanine Nucleotide Exchange Factors 0
VEGFA protein, human 0
Vascular Endothelial Growth Factor A 0
Vegfaa protein, zebrafish 0
Zebrafish Proteins 0
rac1a protein, zebrafish 0
Placenta Growth Factor 144589-93-5
FLT1 protein, zebrafish EC 2.7.10.1
Vascular Endothelial Growth Factor Receptor-1 EC 2.7.10.1
Protein Serine-Threonine Kinases EC 2.7.11.1
TRIO protein, human EC 2.7.11.1
rac1 GTP-Binding Protein EC 3.6.5.2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5319

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Auteurs

Alina Klems (A)

Department of Cell and Developmental Biology, Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT), Fritz Haber Weg 4, 76131, Karlsruhe, Germany.

Jos 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.
ORCID: 0000-0001-8077-1371

Anne S 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.

Raphael Wild (R)

Department of Cell and Developmental Biology, Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT), Fritz Haber Weg 4, 76131, Karlsruhe, Germany.

Julia Hammer (J)

Department of Cell and Developmental Biology, Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT), Fritz Haber Weg 4, 76131, Karlsruhe, Germany.

Melanie Merkel (M)

Department of Cell and Developmental Biology, Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT), Fritz Haber Weg 4, 76131, Karlsruhe, Germany.

Laura Derenbach (L)

Department of Cell and Developmental Biology, Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT), Fritz Haber Weg 4, 76131, Karlsruhe, Germany.

Laetitia Préau (L)

Department of Cell and Developmental Biology, Institute of Zoology (ZOO), Karlsruhe Institute of Technology (KIT), Fritz Haber Weg 4, 76131, Karlsruhe, Germany.

Rabea 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.
ORCID: 0000-0002-2936-0400

Irina 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.

Stefan 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.

Ramon 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.
ORCID: 0000-0003-4217-2014

Sascha 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.
ORCID: 0000-0002-4794-3693

Riikka Kivelä (R)

Stem Cells and Metabolism Research Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, and Wihuri Research Institute, Helsinki, Finland.
ORCID: 0000-0002-2686-8890

Kari Alitalo (K)

Translational Cancer Medicine Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, and Wihuri Research Institute, Helsinki, Finland.
ORCID: 0000-0002-7331-0902

Christian 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.
ORCID: 0000-0002-3611-1218

Jaap D 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.
ORCID: 0000-0003-0054-7949

Ferdinand 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.
ORCID: 0000-0001-6195-7672

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › The GEF Trio controls endothelial cell size...
questionsmedicales.fr › Stades d'organismes › Organismes génétiquement modifiés › Animal génétiquement modifié › The GEF Trio controls endothelial cell size...
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