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Description

Prolow-density lipoprotein receptor-related protein 1 (UniProt Q07954, also known as A2MR, Alpha-2-macroglobulin receptor, APOER, Apolipoprotein E receptor, CD91, LRP-1) is encoded by the LRP1 (also known as A2MR, APR) gene (Gene ID 4035) in human. LRP1 is an LDLR family member expressed by vascular endothelial cells forming the blood-brain barrier (BBB), vascular mural cells (pericytes and vascular smooth muscle cells (VSMCs)), neurons, and astrocytes. LRP1 recognizes and mediates the endocytosis of more than 40 different ligands, including apolipoprotein E (apoE), APP and Abeta. LRP1 is the primary receptor mediating transport of Abeta across the BBB into circulation, thereby clearing it from the brain. LRP1 is synthesized with a signal peptide sequence (a.a. 1-19), posttranslational cleavage yields a soluble form (sLRP1) and a cell surface-bound form composed of an 515 kDa extracellular alpha-chain (LRP-515) and a 85 kDa single-transmembrane (a.a. 4420-4444) beta-chain (LRP-85) that contains the 100-amino intracellular domain (LRPICD, a.a. 4445-4544). BACE-1, ADAM-10, ADAM-12, ADAM-17, MT1-MMP, and t-PA are shown to be involved in the shedding of LRP1 to produce sLRP1.