| First Author | Xian X | Year | 2017 |
| Journal | Elife | Volume | 6 |
| PubMed ID | 29144234 | Mgi Jnum | J:255005 |
| Mgi Id | MGI:6111033 | Doi | 10.7554/eLife.29292 |
| Citation | Xian X, et al. (2017) LRP1 integrates murine macrophage cholesterol homeostasis and inflammatory responses in atherosclerosis. Elife 6:e29292 |
| abstractText | Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional cell surface receptor with diverse physiological roles, ranging from cellular uptake of lipoproteins and other cargo by endocytosis to sensor of the extracellular environment and integrator of a wide range of signaling mechanisms. As a chylomicron remnant receptor, LRP1 controls systemic lipid metabolism in concert with the LDL receptor in the liver, whereas in smooth muscle cells (SMC) LRP1 functions as a co-receptor for TGFbeta and PDGFRbeta in reverse cholesterol transport and the maintenance of vascular wall integrity. Here we used a knockin mouse model to uncover a novel atheroprotective role for LRP1 in macrophages where tyrosine phosphorylation of an NPxY motif in its intracellular domain initiates a signaling cascade along an LRP1/SHC1/PI3K/AKT/PPARgamma/LXR axis to regulate and integrate cellular cholesterol homeostasis through the expression of the major cholesterol exporter ABCA1 with apoptotic cell removal and inflammatory responses. |
