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Description

Prolow-density lipoprotein receptor-related protein 1 (UniProt: Q07954, also known as LRP-1, Alpha-2-macroglobulin receptor1, A2MR, Apolipoprotein E receptor, APOER, CD91) is encoded by the LRP1 (also known as A2MR, APR) gene (Gene ID: 4035) in human. LRP-1 is expressed in most tissues, but is abundant in liver, brain, and lung. LRP1 is synthesized with a signal peptide sequence (a.a. 1-19) and is processed in trans-Golgi network by furin to generate a 515 kDa alpha subunit and an 85 kDa beta subunit. The alpha and beta subunits are non-covalently linked during LRP1 transport to the cell membrane. LRP-1 recognizes and mediates the endocytosis of more than 40 different ligands, including apolipoprotein E (ApoE), APP and amyloid beta. It is the primary receptor mediating transport of amyloid beta peptides across the blood-brain barrier into circulation, thereby clearing them from the brain. LRP-1 is required for early embryonic development and is involved in cellular lipid homeostasis and plasma clearance of chylomicron remnants and activated LRPAP1 (alpha 2-macroglobulin). Excessive copper accumulation in the brain has been linked with reduced LRP-1 mediated clearance of amyloid beta peptides across the blood brain barrier, which may contribute to complications of Alzheimer's disease.