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

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 furthe

SUBMITTER: Driessen RCH 

PROVIDER: S-EPMC6256362 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature