Dual pathways for the uptake of rat asialotransferrin by rat hepatocytes.
Studies of the interaction of rat asialotransferrin with rat hepatocytes at 4 degrees C showed that the protein binds to two types of receptor on these cells--to 31,000 transferrin receptors with a Ka of 1.9 x 10(7) liters . mol-1 and to 110,000 asialoglycoprotein receptors with a Ka of 1.4 x 10(6) liters . mol-1. The uptake of the protein by the cells at 37 degrees C is mediated by both receptors simultaneously. Binding to the asialoglycoprotein receptor was abolished by the addition of excess asialoorosomucoid and, under these conditions asialotransferrin, taken into the cells via the transferrin receptor, was subsequently released from the cells undegraded, an event also observed when the uptake of holotransferrin was examined in similar studies. Addition of excess unlabeled transferrin prevented uptake of asialotransferrin via the transferrin receptor and internalization was then mediated solely by the asialoglycoprotein receptor. Ligand subsequently released from the cells after endocytosis via this receptor was found to be degraded, with 80% soluble in trichloroacetic acid, a proportion similar to that observed during release of asialoorosomucoid from the cells. These results indicate that rat asialotransferrin is processed by the asialoglycoprotein uptake pathway in the same way as observed with other ligands. Release from the cells of undegraded asialotransferrin occurred only after endocytosis via the transferrin receptor.
D000818:Animals; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D001692:Biological Transport; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism; D011990:Receptors, Transferrin; D012156:Reticulocytes / Q000378:metabolism; D013997:Time Factors; D014168:Transferrin / Q000031:analogs & derivatives* / Q000378:metabolism
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D014168:Transferrin; C017031:asialotransferrins