Biosynthesis and Processing of Low Density Lipoprotein (LDL) Receptor in the Fibroblasts of Internalization-Defective Type Familial Hypercholesterolemia

Previously we found a case of homozygous familial hypercholesterolemia with a defect in internalization of low density lipoprotein (LDL). Her LDL receptors were able to bind LDL normally but failed to cluster in coated pits. Hence transport of LDL into the cell could not occur in this case.In the present study were analyzed the biosynthesis of LDL receptor in fibroblasts of this patient by labeling with 35S-methionine followed by immunoprecipitation with anti-LDL receptor antibody.The patient's cells synthesized LDL receptor with a molecular weight slightly smaller than normal in SDS polyacrylamide gel electrophoresis. Strikingly, a large portion of the synthesized receptors were secreted into the medium. It is supposed that the secretion was caused by the deletion of a part of the peptide chain near carboxy terminal which is necessary to anchor the receptor protein in the cytoplasmic membrane.