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Description

Prolow-density lipoprotein receptor-related protein 1 (UniProt Q07954, also known as A2MR, Alpha-2-macroglobulin receptor, APER, Apolipoprotein E receptor, CD19. LRP-1) is encoded by the LRP1 (also known as A2MR, APR) gene (Gene ID: 4035) in human. LRP-1 is single pass type I membrane protein that is expressed in most tissues, but is abundant in liver, brain, and lung. It serves as a major VSMC receptor with a crucial role in maintaining vessel wall integrity and its expression in adult smooth muscle cells is shown to be essential for maintaining a contractile phenotype. LRP1 is synthesized with a signal peptide sequence (aa 1-19) and is processed in trans-Golgi network by Furin to generate a 515 kDa a subunit and an 85 kDa b subunit that contains the 100-amino intracellular domain (LRPICD, aa 4445-4544). The a and b subunits are non-covalently linked during LRP1 transport to the cell membrane. LRP1 recognizes and mediates the endocytosis of more than 40 different ligands, including apolipoprotein E (ApoE), APP and amyloid b. It is the primary receptor mediating transport of amyloid b peptides across the blood-brain barrier into circulation, thereby clearing them from the brain. LRP1 is required for early embryonic development and is involved in cellular lipid homeostasis and plasma clearance of chylomicron remnants and activated LRPAP1 (a2-macroglobulin). Excessive copper accumulation in the brain has been linked with reduced LRP1 mediated clearance of amyloid b peptides across the blood brain barrier, which may contribute to complications of Alzheimer's disease.