Molecular Mechanisms of Endocytic Sorting

Abstract

During the past few years, a general consensus has been reached concerning the basic pathway of receptor-mediated endocytosis in mammalian cells (Helenius et al., 1983; Hopkins, 1983; Brown et al., 1983; Mel lman et al., 1986). The basic features of this pathway include: the binding of extracellular ligands to specific receptors on the plasma membrane, the accumulation and subsequent internalization of the receptor-ligand complex in clathrin coated pits and coated vesicles, and the delivery of these complexes to endosomes -- a heterogeneous population of uncoated vesicles and associated tubules (Marsh et al., 1986) -- whose mildly acidic internal pH favors the dissociation of ligand from receptor. Newly vacated receptors then return to the cell surface to participate in subsequent rounds of ligand uptake, while ligands are generally transported to lysosomes where they are degraded. The dissociation and “sorting” of receptor from ligand in endosomes represents one of the most critical and most recently appreciated steps in the endocytic pathway. In this paper, we will review some of our recent work on the isolation and functional characterization of endosomes. In addition, we will discuss some of the properties and the cDNA cloning of a macrophage Fc receptor for IgG, the study of which has begun to provide some insight into the control of membrane traffic in endosomes at the molecular level.