Shear stress induces expression, intracellular reorganization and enhanced Notch activation potential of Jagged1

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Driessen RCH, Stassen OMJA, Sjöqvist M, Rodriguez FS, Grolleman J, Bouten CVC, Sahlgren CM
Publisher: ROYAL SOC CHEMISTRY
Publication year: 2018
Journal: Integrative Biology
Journal acronym: INTEGR BIOL-UK
Volume number: 10
Issue number: 11
Start page: 719
End page: 726
Number of pages: 8
ISSN: 1757-9694


Abstract

Notch signaling and blood flow regulate vascular formation and maturation, but how shear stress affects the different components of the Notch pathway in endothelial cells is poorly understood. We show that laminar shear stress results in a ligand specific gene expression profile in endothelial cells (HUVEC). JAG1 expression increases while DLL4 expression decreases. Jagged1 shows a unique response by clustering intracellularly six to nine hours after the onset of flow. The formation of the Jagged1 clusters requires protein production, ER export and endocytosis. Clustering is associated with reduced membrane levels but is not affected by Notch signaling activity. Jagged1 relocalization is reversible, the clusters disappear and membrane levels increase upon removal of shear stress. We further demonstrate that the signaling potential of endothelial cells is enhanced after exposure to shear stress. Together we demonstrate a Jagged1 specific shear stress response for Notch signaling in endothelial cells.

Last updated on 2019-24-06 at 05:32