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

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)

Interna författare/redaktörer

Publikationens författare: Driessen RCH, Stassen OMJA, Sjöqvist M, Rodriguez FS, Grolleman J, Bouten CVC, Sahlgren CM
Publiceringsår: 2018
Tidskrift: Integrative Biology
Tidskriftsakronym: INTEGR BIOL-UK
Volym: 10
Nummer: 11
Artikelns första sida, sidnummer: 719
Artikelns sista sida, sidnummer: 726
Antal sidor: 8
ISSN: 1757-9694


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.

Senast uppdaterad 2019-12-11 vid 04:31