Shear stress induces expression, intracellular reorganization and enhanced Notch activation potential of Jagged1. Issue 11 (17th October 2018)

• Record Type: Journal Article
• Authors: Driessen, R. C. H.; Stassen, O. M. J. A.; Sjöqvist, M.; Suarez Rodriguez, F.; Grolleman, J.; Bouten, C. V. C.; Sahlgren, C. M.
• Is Part Of: Integrative biology. Volume 10:Issue 11(2018)
• Page Start: 719
• Page End: 726
• Publication Date: 2018-10-17
• Subjects: Biology -- Periodicals; Technology -- Periodicals; Biological systems -- Periodicals; 570.5
• DOI: 10.1039/c8ib00036k
• Languages: English
• ISSNs: 1757-9694

Abstract

Abstract : Shear stress induces a ligand specific Jagged1 response and enhanced signal sending potential in endothelial cells. 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.