The endocytosis of oxidized LDL via the activation of the angiotensin II type 1 receptor

Arrestin-dependent activation of a G-protein-coupled receptor (GPCR) triggers endocytotic internalization of the receptor complex. We analyzed the interaction between the pattern recognition receptor (PRR) lectin-like oxidized low-density lipoprotein (oxLDL) receptor (LOX-1) and the GPCR angiotensin II type 1 receptor (AT1) to report a hitherto unidentified mechanism whereby internalization of the GPCRmediates cellular endocytosis of the PRR ligand. Using geneticallymodified Chinese hamster ovary cells, we found that oxLDL activates Gai but not the G alpha q pathway of AT1 in the presence of LOX-1. Endocytosis of the oxLDL-LOX-1 complex through the AT1-beta-arrestin pathway was demonstrated by real-time imaging of the membrane dynamics of LOX-1 and visualization of endocytosis of oxLDL. Finally, this endocytotic pathway involving GPCR kinases (GRKs), beta-arrestin, and clathrin is relevant in accumulating oxLDL in human vascular endothelial cells. Together, our findings indicate that oxLDL activates selective G proteins and beta-arrestin-dependent internalization of AT1, whereby the oxLDL-LOX-1 complex undergoes endocytosis.

Automated summary

The study revealed a previously unidentified mechanism whereby internalization of GPCR mediates cellular endocytosis of a specific PRR ligand. OxLDL activates selective G proteins and beta-arrestin-dependent endocytosis pathway, leading to accumulation in human vascular endothelial cells.