Uptake of mannose-terminated glycoproteins in isolated rat liver cells. Evidence for receptor-mediated endocytosis in hepatocytes.
Even though most of the hepatic binding capacity for mannose-terminated glycoproteins has previously been shown to reside in the hepatocytes (not in the non-parenchymal cells), detailed evidence for the specific uptake of mannose-terminated ligands has been lacking. In the present studies, yeast invertase, a large glycoprotein (Mr 270 000) containing about 50% mannose, was shown to be taken up into hepatocytes by receptor-mediated endocytosis. The uptake was saturable and could be specifically inhibited by mannosides or by a Ca2+ chelator. The asialo-glycoprotein receptor was not involved. The low-Mr (13 000) ligand ribonuclease B, which contains a single high-mannose glycan, was not taken up by hepatocytes; however, it was taken up as fast as invertase by non-parenchymal liver cells. After injection of 131I-invertase into a rat in vivo, about one-half of the labelled protein was recovered in the hepatocytes. On a per-cell basis, each endothelial cell contained 3-4 times as much radioactivity as did the hepatocytes. On fractionation of hepatocytes in sucrose gradients, invertase showed a different intracellular distribution from that of asialo-fetuin, in that invertase moved much faster into that region of the gradient where the lysosomes were recovered. This indicates that invertase and asialo-fetuin are not transported intracellularly by identical mechanisms.
D000818:Animals; D001692:Biological Transport; D002499:Centrifugation, Density Gradient; D004705:Endocytosis; D004727:Endothelium / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012260:Ribonucleases / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D013696:Temperature; D043324:beta-Fructofuranosidase
D012260:Ribonucleases; C029600:ribonuclease B; D006026:Glycoside Hydrolases; D043324:beta-Fructofuranosidase