Receptor-mediated endocytosis and the cellular uptake of low density lipoprotein

During receptor-mediated endocytosis various extracellular nutritional and regulatory molecules bind to plasma membrane receptors and rapidly enter target cells. In many systems (including those for certain plasma transport proteins, protein hormones, glycoproteins, toxins and viruses, and other plasma proteins) the receptors cluster in discrete regions of the surface membrane called coated pits, which invaginate into the cell to form endocytic vesicles. The extracellular ligand enclosed in the endocytic vesicle is delivered to intracellular sites, frequently to lysosomes, where it is degraded. In one system of receptor-mediated endocytosis, namely the one for plasma low density lipoprotein (LDL), the receptor functions to internalize LDL. The LDL is delivered to lysosomes where it is degraded and its cholesterol is released for use in the synthesis of membranes, steroid hormones and bile acids. Three recent advances in the LDL receptor system are reviewed: (1) the development of a method for purifying the receptor to apparent homogeneity and the demonstration that the LDL-binding site is contained within a glycoprotein of relative molecular mass 164000 and an acidic isoelectric point of 4.6; (2) the production of monoclonal antibodies directed against the receptor and the use of these antibodies as probes for receptor-mediated endocytosis; and (3) the use of monovalent carboxylic ionophores (such as monensin) to demonstrate by immunofluorescence that the LDL receptor enters the cell together with LDL, after which it recycles to the surface.