VE‐cadherin N‐glycosylation modified by N‐acetylglucosaminyltransferase V regulates VE‐cadherin–β‐catenin interaction and monocyte adhesion

New Findings What is the central question of this study? Inflammation‐induced monocyte adhesion is the initiator of most vascular diseases. The underlying mechanisms that mediate monocyte adhesion remain to be clarified fully. What is the main finding and its importance? N ‐acetylglucosaminyltransferase V (GnT‐V)‐mediated N ‐glycosylation of VE‐cadherin regulates the dissociation of the VE‐cadherin–β‐catenin complex to modulate monocyte adhesion, but GnT‐V overexpression cannot rescue monocyte adhesion induced by interleukin‐1β. This study clarified the molecular mechanism of VE‐cadherin in regulating the monocyte adhesion process. Abstract Monocyte adhesion is a crucial step in the initial stage of atherosclerosis, and dysfunction of VE‐cadherin has been reported to be involved in this process. Our group previously found that VE‐cadherin and its binding protein, β‐catenin, were modified by sialylation, and the levels of sialylation were decreased in pro‐inflammatory cytokine‐treated human umbilical vein EA.hy926 cells. In this study, we confirmed that the sugar chains of VE‐cadherin were modified by N ‐acetylglucosaminyltransferase V (GnT‐V). We showed that the levels of GnT‐V and β1,6‐ N ‐acetylglucosamine on the VE‐cadherin were reduced in the presence of interleukin‐1β, whereas the level of monocyte transendothelial migration was increased. Moreover, the interaction between VE‐cadherin and β‐catenin was increased, accompanied by an increased accumulation of degradative VE‐cadherin and cytoplasmic β‐catenin, indicating impairment of cell–cell junctions after interleukin‐1β treatment. Furthermore, GnT‐V short hairpin RNA and overexpression analysis confirmed that glycosylation of VE‐cadherin was modified by GnT‐V in EA.hy926 cells, which contributed to the monocyte–endothelial adhesion process. Taken together, these results suggest that the function of VE‐cadherin in facilitating monocyte adhesion might result from the decreasing GnT‐V expression and disorder of GnT‐V‐catalysed N ‐glycosylation. Our study clarified the molecular mechanism of VE‐cadherin in regulation of the monocyte adhesion process and provided new insights into the post‐transcriptional modifications of VE‐cadherin.