Ligand-induced endocytosis of the asialoglycoprotein receptor: evidence for heterogeneity in subunit oligomerization.

The hepatic asialoglycoprotein receptor, a noncovalent hetero-oligomer of two subunits, is a constitutively cycling endocytic receptor. However, the ligand asialoorosomucoid caused downregulation of up to 40% of surface binding sites and a twofold increase in internalization rate. This was not the result of receptor crosslinking, since monovalent ligands had the same effect. Ligand binding thus appears to transmit a signal to the cytosolic portion of the receptor not unlike in signaling receptors. The two subunits were endocytosed at different average rates lower than that of ligand, indicating heterogeneity in oligomer formation and potentially in ligand specificity.