Endocytosis and Function of the Hepatic Asialoglycoprotein Receptor

Abstract

When desialylated, plasma glycoproteins, including some hormones, become ligands for recognition by this galactosyl (Gal) receptor (Ashwell and Harford, 1982; Schwartz, 1984). The interaction of the receptor with most ligands is of high affinity; dissociation constants are in the nM range. The ligand used most predominantly is desialylated α_l-acid glycoprotein (also called orosomucoid), which is a soluble-plasma acute-phase protein. Neoglycoproteins, synthetic polymers, or solid surfaces containing a sufficient density of Gal groups will also be bound by the receptor. The receptor is found only in hepatocytes. Only 10–25% of the total cellular receptors are on the cell surface, while 75–90% are inside the cell. There are about a half-million receptors per cell. The receptor recycles both in vivo and in vitro. Ligand dissociation occurs below pH 6, and Ca²⁺ is required for binding. Oligosaccharide binding to the receptor requires a relatively high Ca²⁺ concentration; the apparent K_d is approximately 1.5 mM, and about 3Ca²⁺ are bound/polypeptide chain of the rabbit receptor (Andersen et al., 1982). Very little ligand binding (<1%) occurs in the absence of Ca²⁺ or the presence of chelators such as ethylenediaminetetraacetic acid (EDTA). This fact is often used as the basis for most easily determining the nonspecific binding of radiolabeled ligands.