A mutation that impairs the ability of lipoprotein receptors to localise in coated pits on the cell surface of human fibroblasts.
Low density lipoprotein is taken up by cultured human fibroblasts through an endocytic process that requires the binding of the lipoprotein to specific receptors located in coated pits on the cell surface. The coated pits are discrete segments of the plasms membrane that can undergo rapid invagination to form coated endocytic vesicles. In one form of the human genetic disorder familial hypercholesterolaemia, the responsible mutation produces altered lipoprotein receptors that lack the ability to become incorporated into coated pits. Instead, these mutant receptors are scattered at random over the entire plasma membrane. Becuase of their mislocation on the cell surface, the mutant lipoprotein receptors are unable to carry their bound lipoprotein into the cell. The occurrence of this 'receptor mislocation mutation' provides strong evidence for the role of the coated pit in the receptor-mediated uptake of lipoproteins. The data also have implications for the structure and assembly of plasma membranes in mammalian cells.
D000483:Alleles; D001345:Autoradiography; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D004705:Endocytosis; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism*
D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D011955:Receptors, Drug