An in vivo Method for Determination of Endosomal Distribution of Both Ligand and Asialoglycoprotein Receptor in Rat Liver

Introduction Alcoholic liver injury is a significant medical problem throughout the world. Protein trafficking pathways, including endocytosis, appear to be especially susceptible to the deleterious effects of alcohol. Using the asialoglycoprotein receptor (ASGPR) as a model, we have studied ethanol-induced alterations in the process of receptormediated endocytosis (RME). The ASGPR, a hepatocytespecific receptor, binds proteins that have lost their terminal sialic acid moiety and have exposed galactose or Nacetylgalactosamine moieties [1]. During RME many extracellular ligands are bound by specific cell surface receptors, such as the ASGPR, and internalized via a clathrin-coated pit pathway [2]. In the endocytotic pathway, the lumen of the endosome becomes acidic allowing the receptor-ligand complexes to dissociate. The separated receptors and ligands can either be targeted for degradation in lysosomes or recycled back to the cell surface. Endosomal trafficking from the cell surface to the final destination in the cell is an extremely complex process that is still not completely understood.