The low density lipoprotein receptor gene family is a group of endocytic receptors that mediate the uptake of lipoproteins. There are nine LDL receptors in mammals, LDL, VLDL, ApoER2, LRP5, LRP6, MEGF7, LRP1, LRP1B and Megalin, all of which share common structural motifs for receptor-mediated endocytosis. The extracellular domains contain clusters of complement-type repeats and epidermal growth factor precursor domains which are essential for ligand binding and pH-dependent release of ligands in endosomes respectively. The cytoplasmic tails contain recognition sites for cytosolic adaptor protein, such as those that regulate internalization via clathrin coated pits.
The prototype of this family is the LDL receptor that mediates cellular uptake of cholesterol-rich lipoproteins. Mutations in this receptor result in accumulation of LDL particles in the circulaton, causing in hypercholesterolemia. Cholesterol homeostasis is the role that is commonly associated with members of the LDL receptor family. However, knockout studies have uncovered a range of additional activities. The LDL receptors also bind to proteases, signaling molecules and heat shock proteins, resulting in endocytic uptake, but also affecting other cellular processes including migration, pericellular proteolysis, synaptic plasticity and antigen presentation.
More than a decade ago, apolipoprotein E4 (ApoE4) was identified as a primary genetic risk factor for Alzheimer's disease. LDL, LRP1, VLDL and ApoER2 receptors have all been identified as brain apoE receptors. LDL is also directly involved in atherosclerosis. When LDL-cholesterol in the blood becomes oxidized it causes damage to the artery wall and initiates an immune response that results in the formation of the atherosclerotic plaque.View all products for LDL Receptors »
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