Receptor-mediated biliary transport of immunoglobulin A and asialoglycoprotein: sorting and missorting of ligands revealed by two radiolabeling methods.
In the rat, all receptor-bindable immunoglobulin A (IgA), and 1-4% of injected asialoglycoprotein (ASG), are transported from blood to bile intact. The major fraction of the ASG is degraded in hepatic lysosomes. The study described here was designed to elucidate the sorting that occurs in hepatocytes subsequent to receptor binding of ligands not sharing the same fate. We show that conjugation of protein with the Bolton and Hunter reagent can be used as a probe for the lysosomal pathway, since 50% of the reagent is released into bile after lysosomal degradation of internalized protein. Radiolabeling by iodine monochloride was alternatively used to follow the direct pathways that deliver intact IgA and ASG to bile. After intravenous injection of labeled proteins, first intact ASG and IgA, and then radioactive catabolites from degraded protein, were released into bile. No proteolytic intermediates were detected, and the transport of IgA or ASG directly to bile was not affected by the lysosomal protease inhibitor leupeptin. These observations indicate that divergence of the direct biliary transport pathways from the degradation pathway occurs at a stage preceding delivery to lysosomes, possibly at the cell surface. Competition studies showed that all three pathways (including the biliary transport of intact ASG) are receptor mediated, but even at supersaturating doses the uptake and processing of IgA and ASG occur independently. We propose that IgA and ASG receptors are not frequently in juxtaposition on the plasma membrane, but that ASG, after binding to its receptor, is occasionally missorted into the biliary transport pool.
D000818:Animals; D001212:Asialoglycoproteins; D001646:Bile / Q000378:metabolism*; D002451:Cell Compartmentation; D004705:Endocytosis; D006023:Glycoproteins / Q000378:metabolism*; D007070:Immunoglobulin A / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism
D001212:Asialoglycoproteins; D006023:Glycoproteins; D007070:Immunoglobulin A; D011956:Receptors, Cell Surface