Ubiquitination of VE-cadherin regulates inflammation-induced vascular permeability in vivo

ABSTRACT: VE-cadherin is a major component of the cell adhesion machinery which provides integrity and plasticity of the barrier function of endothelial junctions. Here, we analyze whether ubiquitination of VE-cadherin is involved in the regulation of the endothelial barrier in inflammation in vivo. We show that histamine and thrombin stimulate ubiquitination of VE-cadherin in HUVEC, which is completely blocked if the two lysine residues K626 and K633 are replaced by arginine. Similarly, these mutations block histamine-induced endocytosis of VE-cadherin. We describe two knock-in mouse lines with endogenous VE-cadherin being replaced by either a VE-cadherin-K626/633R or a VE-cadherin-KallR mutant, where all seven lysine residues are mutated. Mutant mice are viable, healthy and fertile with normal exp

SUBMITTER: Mr. Markus Wilkens 

PROVIDER: S-SCDT-10_1038-S44319-024-00221-7 | biostudies-other |

REPOSITORIES: biostudies-other