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

Klems, Alina; van Rijssel, Jos; Ramms, Anne S.; Wild, Raphael; Hammer, Julia; Merkel, Melanie; Derenbach, Laura; Préau, Laetitia; Hinkel, Rabea; Suarez-Martinez, Irina; Schulte-Merker, Stefan; Vidal, Ramon; Sauer, Sascha; Kivelä, Riikka; Alitalo, Kari; Kupatt, Christian; van Buul, Jaap D.; le Noble, Ferdinand

Abstract (englisch):
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.

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Verlagsausgabe §
DOI: 10.5445/IR/1000126133
Veröffentlicht am 13.11.2020
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische und Chemische Systeme (IBCS)
Zoologisches Institut (ZOO)
Publikationstyp Zeitschriftenaufsatz
Publikationsmonat/-jahr 12.2020
Sprache Englisch
Identifikator ISSN: 2041-1723
KITopen-ID: 1000126133
Erschienen in Nature Communications
Band 11
Heft 1
Seiten Article: 5319
Vorab online veröffentlicht am 21.10.2020
Nachgewiesen in Scopus
Web of Science
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