Trafficking of asialoglycoproteins and the asialoglycoprotein receptor.

Thus, the ASGP-R, a liver parenchymal cell-specific receptor, directs the receptor-mediated endocytosis of galactose-terminal glycoprotein ligands from the circulation into the liver cell, as seen in Figure 3. Following binding at the cell surface and internalization, the major pathway of ligand and receptor movement in the cell involves trafficking to CURL. Here acidification dissociates ligand from receptor, allowing the receptor to recycle back to the cell surface and directing ligand on to lysosomal degradation. Alternative routes of ligand movement, such as the slow ligand-recycling pathway, have recently been observed, and it is tempting to speculate that this occurs by the TGR. There is now ample biochemical, kinetic, and morphological evidence to support both rapid receptor recycling as well as slow receptor recycling associated with ligand recycling. The importance of CURL in the dissociation and segregation of ligand and receptors as well as in receptor recycling and of the recently described TGR are now evident. In addition, the ASGP-R of the hepatocyte has provided interesting parallels and contrasts to other receptor systems that participate in receptor-mediated endocytosis in liver parenchymal cells (155).