Evidence that recycling of low density lipoprotein receptors does not depend on delivery of receptors to lysosomes

Abstract

Summary The rates of endocytosis and degradation of low density lipoproteins by human fibroblasts were determined as a function of temperature. At temperatures below 20°C, degradation of 125 I-labeled low density lipoprotein was totally inhibited while endocytosis still occurred albeit at a slower rate than at 37°C. At 20°C, the amount of low density lipoprotein endocytosed during 5 hours was approximately 8 times greater than the amount of low density lipoprotein bound to cell surface receptors. The carboxylic ionophore monensin caused a significant reduction (30%) of cell-surface low density lipoprotein receptors after 20 minutes at 20°C. These results indicate that receptor recycling occurs at temperatures (⩽20°C) at which low density lipoprotein degradation is blocked. Since the inhibition of degradation is probably due to an inhibition of lysosome-endosome fusion, we conclude that recycling of low density lipoprotein receptors does not depend on the delivery of receptors to lysosomes and that dissociation of the ligand from its receptor occurs at an extralysosomal location.