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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Klems A,van Rijssel J,Ramms AS,Wild R,Hammer J,Merkel M,Derenbach L,Préau L,Hinkel R,Suarez-Martinez I,Schulte-Merker S,Vidal R,Sauer S,Kivelä R,Alitalo K,Kupatt C,van Buul JD,le Noble F

doi

10.1038/s41467-020-19008-0

subject

Has Abstract

pub_date

2020-10-21 00:00:00

pages

5319

issue

1

issn

2041-1723

pii

10.1038/s41467-020-19008-0

journal_volume

11

pub_type

杂志文章

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