Distinction between binding and endocytosis of human asialo-transferrin by the rat liver.
The ability of the rat liver to bind and endocytose human asialo-transferrin was investigated in vivo. Asialo-transferrin was separated from incompletely desialylated transferrin and neuraminidase by chromatography before being labelled with (125)I. Plasma radioactivity curves and hepatic radioactivity contents measured over a 1270-fold dose range led to the following observation. At the lowest dose (0.4mug/100g body wt.), the distribution of asialo-transferrin between plasma and liver resembled a reversible reaction reaching equilibrium in approx. 20min. After 35min, 93% of the dose was recovered with the plasma and liver as protein-bound radioactivity. Most of the asialo-transferrin associated with the liver could be displaced by asialo-orosomucoid, indicating that binding of asialo-transferrin to the galactose-specific lectin on the plasma membrane of hepatocytes was not followed by a signal for endocytosis. A range of doses, up to an average of 509.2mug of asialo-transferrin per 100g body wt., resulted in progressive increments in asialo-transferrin catabolism, as evidenced by lower dose recoveries and increased concentrations of non-protein-associated radioactivity in the liver and plasma volume. These observations indicate that binding and endocytosis of human asialo-transferrin by the rat hepatocyte are distinct phenomena. Individual asialo-transferrin molecules, although readily bound by the hepatic lectin, lack either the quantity or spacing of terminal galactose residues necessary for triggering endocytosis. Although endocytosis is induced by several asialo-transferrin molecules acting synergistically, preliminary experiments with asialo-glycopeptides and other substances have so far failed to provide further insight into the chemical basis of the signal for endocytosis.
D000818:Animals; D004705:Endocytosis; D006020:Glycopeptides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011485:Protein Binding; D051381:Rats; D013395:Sucrose / Q000494:pharmacology; D014168:Transferrin / Q000031:analogs & derivatives* / Q000378:metabolism
D006020:Glycopeptides; D014168:Transferrin; D013395:Sucrose