Asialoglycoprotein receptors in rat liver nodules

The asialoglycoprotein (ASGP) receptor, binding and internalizing glycoproteins exposing terminal galactose or N-acetylgalactosamine residues, was compared in normal liver, regenerating liver and liver nodules. The total cellular content of ASGP binding sites was reduced to 50 and 40% in regenerating liver and liver nodules respectively, compared to the level in normal liver. The ASGP receptor was heterogeneously distributed in subcellular fractions, with the highest enrichment (16-fold) found in a low-density membrane fraction (LDMF), enriched in endosomes and Golgi complex membranes. The subcellular distribution pattern was similar in the three different liver tissues, except that the relative enrichment in LDMF was less pronounced in regenerating liver (13-fold) and even less in liver nodules (5-fold). Scatchard analysis of the binding data indicated that the receptor populations in all liver tissues were homogeneous with dissociation constants in the range of 0.12-0.47 nM. The difference in ASGP receptor binding activity was not found to be the result of an increased occupancy with endogenous ligand. In vivo endocytosis of [125I]asialo-orosomucoid ([125I]ASOR) showed a reduction in the amount of internalized ligand in liver nodules, well correlated with the reduced number of binding sites compared to normal liver. However, a slower than normal intracellular metabolism of internalized ligand in the nodules was indicated. Bifunctional cross-linking experiments showed [125I]ASOR--receptor complexes of Mr 250,000, 110,000 and 85,000 in normal and regenerating liver, whereas in liver nodules only the Mr 85,000 was seen. It is concluded that ASGP binding activity is reduced in regenerating liver and in liver nodules. This reduction was manifested predominantly in membranes derived from the Golgi complex, in endocytic vesicles and at the cell surface. The slower than normal rate of decay of the internalized ligand in liver nodules is suggested to be the result of alterations in ligand dissociation and receptor recycling processes. Furthermore, the absence of high molecular cross-linkable [125I]ASOR--receptor complexes in liver nodules may reflect an alteration in receptor oligomerization.