Endocytosis of lysosomal enzymes by non-parenchymal rat liver cells. Comparative study of lysosomal-enzyme uptake by hepatocytes and non-parenchymal liver cells.
Cultured non-parenchymal rat liver cells internalize human urine alpha-N-acetylglucosaminidase, human skin beta-N-acetylglucosaminidase and pig kidney alpha-mannosidase. Different heat-stabilities of endocytosed and endogenous alpha-mannosidase activity provided indirect evidence that the increase in intracellular activity resulted from uptake. The high efficiency and the saturation kinetics of uptake indicated that these enzymes become internalized by adsorptive endocytosis. Competition experiments with glycoproteins bearing known carbohydrates at their non-reducing terminals, with mannans, methyl glycosides and monosaccharides, established that the uptake of these three lysosomal enzymes is mediated by the binding to cell-surface receptors that recognize mannose and N-acetylglucosamine residues. The decreased uptake after treatment of these enzymes with either beta-N-acetylglucosaminidase or alpha-mannosidase was in accordance with the results of the inhibition experiments. Removal of oligosaccharides of the high-mannose type by treatment with endoglucosaminidase H inhibited uptake almost completely, suggesting that the sugars recognized by cell-surface receptors of non-parenchymal liver cells are located in the outer core of these oligosaccharides. A comparison of the uptake of these three lysosomal enzymes by parenchymal and non-parenchymal rat liver cells indicates that infused alpha-N-acetylglucosaminidase is taken up preferentially by hepatocytes, whereas alpha-mannosidase and beta-N-acetylglucosaminidase are localized predominantly in non-parenchymal rat liver cells.
D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D002241:Carbohydrates / Q000494:pharmacology; D002478:Cells, Cultured; D004705:Endocytosis / Q000187:drug effects; D006023:Glycoproteins / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D008247:Lysosomes / Q000201:enzymology*; D008361:Mannosidases / Q000378:metabolism; D051381:Rats
D002241:Carbohydrates; D006023:Glycoproteins; D006026:Glycoside Hydrolases; D008361:Mannosidases; D000118:Acetylglucosaminidase