A cell surface receptor (low density lipoprotein receptor) that mediates the endocytosis of LDL by cells. Mutations lead to abnormal serum levels of LDL and hypercholesterolaemia. LDL receptor adaptor protein 1 (LDLRAP1) is the product of the ARH gene, defective in autosomal recessive familial hypercholesterolaemia, which encodes a transmembrane adaptor protein that interacts with the cytoplasmic tail of the LDL receptor, phospholipids, and components of the endocytic machinery (clathrin or AP2). The adaptor is required for internalization of the LDL–LDLR complex, but also for efficient binding of LDL to the receptor. LDL receptor related proteins (LRP) are a family of receptors for multiple ligands that play a wide variety of roles in normal cell function and development. LRP1 (CD91; apolipoprotein E receptor; α2-macroglobulin receptor, 4544 aa) is involved in the endocytic clearance of triglyceride-rich lipoproteins from plasma and the uptake of apolipoprotein E-containing lipoprotein particles by neurons. It also mediates the endocytosis and degradation of secreted amyloid precursor protein and, via α2-macroglobulin, the clearance and degradation of APP-generated β-amyloid. LRP1B has ~60% amino acid identity with LRP1 and binds receptor-associated protein, urokinase plasminogen activator, tissue-type plasminogen activator, and plasminogen activator inhibitor-1. LRP2 (megalin; glycoprotein-330) binds lipoprotein lipase, apolipoprotein E-enriched β-VLDL and apolipoprotein J/clusterin. It is the target antigen of Heymann nephritis and is mutated in Donnai–Barrow syndrome. LRP3 (770 aa) does not bind lipoproteins and its function is unclear. LRP4 has two EGF-like domains as well as similarity with the other LRPs. Mutations in the murine Lrp4 gene are associated with syndactyly. LRP5 (LRP7) is expressed by osteoblasts and can transduce Wnt signalling in vitro. Mutations are associated with osteoporosis–pseudoglioma syndrome, exudative vitreoretinopathy, and various disorders of bone mineralization. LRP6 is a coreceptor for Wnt with LRP5 and mutations are associated with early coronary artery disease and metabolic syndrome. LRP8 (apolipoprotein E receptor 2) is involved in transmitting the extracellular reelin signal to intracellular signalling processes initiated by disabled (DAB1). LDL receptor-related protein associated protein 1 (LRPAP1, α2-macroglobulin receptor-associated protein (MRAP), 357 aa) may function as a chaperone in the synthesis of LRPs.
Subjects: Medicine and Health.