Diacytosis of human asialotransferrin type 3 in the rat liver is due to the sequential engagement of two receptors.
The possible role of transferrin receptors in the diacytosis of human asialotransferrin type 3 (HAsTf-3) by the rat liver was studied in vivo. A trace dose of the ligand was allowed to compete for hepatic binding sites against diferric transferrin, the concentration of which was varied between 5 400- and 18 000-fold. Binding of HAsTf-3 was insensitive to the presence of 2Fe-transferrin in this range, and the liver bound the ligand equally efficiently, regardless of whether it was presented in the holo or apo form. In contrast, pretreating the animals with desialylated bovine submaxillary mucin (2 mg/100 g, 2 min before the dose) prevented the asialotransferrin-liver interaction. These findings indicate that endocytosis of HAsTf-3 is mediated by the Gal/GalNAc-specific lectin and not by transferrin receptors. Although 2Fe-transferrin did not affect binding, it did reduce the half-life of the ligand in the liver, thus suggesting that transferrin receptors play an important role in the exocytic leg of the diacytic cycle. Based on our present and earlier data, a model is proposed in which the engagement of lectin and transferrin receptor in the diacytic cycle is envisaged sequentially so that HAsTf-3 switches receptors at an acidified subcellular site.
D000818:Animals; D001212:Asialoglycoproteins; D004705:Endocytosis; D005260:Female; D006207:Half-Life; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D011990:Receptors, Transferrin; D014168:Transferrin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D001212:Asialoglycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D011990:Receptors, Transferrin; D014168:Transferrin; C017031:asialotransferrins; C028283:diferric transferrin; C037045:galactose-N-acetylgalactosamine receptor