Sorting and recycling of cell surface receptors and endocytosed ligands: The asialoglycoprotein and transferrin receptors

With few exceptions, receptor‐mediated endocytosis of specific ligands is mediated through clustering of receptor‐ligand complexes in coated pits on the cell surface, followed by internalizalion of the complex into endocytic vesicles. During this process, ligand‐receptor dissociation occurs, most probably in a low pH prelysosomal compartment. In most cases the ligand is ultimately directed to the lysosomes, wherein it is degraded, while the receptor recycles to the cell surface. We have studied the kinetics of internalization and recycling of both the asialoglycoprotein receptor and the transferrin receptor in a human hepatoma cell line. By employing both biochemical and morphological/immunocytochemical approaches, we have gained some insight into the complex mechanisms which govern receptor recycling as well as ligand sorting and targeting. We can, in particular, explain why transferrin is exocytosed intact from the cells, while asialoglycoprotcins are degraded in lysosomes. We have also localized the intra‐cellular site at which endocylosed receptor and ligand dissociate.