Rapid release of galactose-terminated ligands after endocytosis by hepatic parenchymal cells: evidence for a role of carbohydrate structure in the release of internalized ligand from receptor.
We have compared the behavior of 125I-labeled asialoorosomucoid (ASOR) and 125I-labeled asialotriantennary glycopeptide (TRI) from alpha-1-protease inhibitor in the perfused rat liver. These two ligands are recognized and internalized by the Gal/GalNAc receptor system of hepatocytes. We found that both ligands could be efficiently degraded when continuously perfused through a liver at 37 degrees C. However, as much as 51% of the internalized 125I-labeled TRI was rapidly (t1/2 = 3 min) released intact into the perfusion medium under conditions that permitted ligand-receptor association. In contrast, ASOR was totally degraded under these conditions. When dissociation was promoted (i.e., in the presence of GalNAc or EGTA), as much as 57% of the internalized ASOR was rapidly released (also intact). In each case, the shorter the initial internalization phase, the greater the proportion of ligand that was subsequently released. Neither the degree of receptor occupancy nor the temperature (16-37 degrees C) during the initial internalization phase influenced the rate or extent of the release process. Electron microscopic localization of internal ASOR-horseradish peroxidase conjugate demonstrated that peripheral endosomes were the major compartment labeled during exocytosis. We conclude that substantial fractions of both ligands rapidly return to the cell surface after internalization, ASOR bound to receptor and most of TRI free from receptor. The remaining ligand molecules enter the lysosomal pathway.
D000818:Animals; D001212:Asialoglycoproteins; D002451:Cell Compartmentation; D004705:Endocytosis; D005089:Exocytosis; D006023:Glycoproteins / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008854:Microscopy, Electron; D009961:Orosomucoid / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology*; D013329:Structure-Activity Relationship; D014168:Transferrin / Q000031:analogs & derivatives / Q000378:metabolism
D001212:Asialoglycoproteins; D006023:Glycoproteins; D009961:Orosomucoid; D011956:Receptors, Cell Surface; D014168:Transferrin; C017030:asialoorosomucoid; C017031:asialotransferrins