Two populations of prelysosomal structures transporting asialoglycoproteins in rat liver.

Analyses by differential centrifugation of liver homogenates from rats that had received 131I-labeled asialoorosomucoid showed that, 1 min after injection, most of the intracellular ligand was associated with a particle that did not sediment at 2.5 X 10(5) g-min. However, by 10 min, undigested ligand became associated with a particle that did sediment at this speed. On analytical ultracentrifugation in sucrose gradients, both kinds of particles exhibited low densities (1.11-1.13 g X ml-1). In contrast to asialoorosomucoid, 125I-labeled asialotransferrin type 3, under noncatabolic conditions, remained largely confined to the nonsedimenting particle regardless of the duration of the study. Induction of catabolism of asialotransferrin was accompanied by the appearance of the ligand in the sedimentable particle. The nonsedimentable particle was separated by immunoadsorption from other subcellular particles contained in the low-density subcellular fraction. The adsorbant , prepared by immobilizing purified antibodies to the Gal/GalN-specific lectin from rat liver on coated polyacrylamide beads, removed 75-80% of the asialoorosomucoid and transferrin binding capacities present, together with a similar portion of the radioligands tested (asialoorosomucoid, asialotransferrin type 3, and human diferric transferrin). Significantly, the sialytransferase activity remained unadsorbed. From these findings, the nonsedimentable particle appears to be involved in the transport of ligands destined to such diverse fates as exocytosis or lysosomal degradation. The sedimentable particle, on the other hand, seems to represent a link between the first particle and the lysosome.