Galactose and N-acetylgalactosamine-specific endocytosis of glycopeptides by isolated rat hepatocytes.
We have examined the kinetics of binding and uptake of iodinated glycoproteins and glycopeptides bearing terminal Gal or GalNAc moieties in an isolated rat hepatocyte system. Asparagine-linked, triantennary complex oligosaccharides with three terminal Gal residues are endocytosed with the same kinetics as asialo-orosomucoid, whereas biantennary, complex oligosaccharides with one or two terminal Gal residues are not endocytosed Glycopeptides bearing as few as four O-glycosidically-linked Gal beta 1, 3GalNAc or GalNAc moieties are also rapidly endocytosed, while glycopeptides with one or two more closely spaced moieties are not endocytosed. All the endocytosable glycoproteins and glycopeptides have similar apparent dissociation constants and a similar number of binding sites on the surface of the intact hepatocyte. The ligand-binding properties of the receptor in the plasma membrane of intact cells differ from those of the solubilized receptor, suggesting that interaction with other as yet undefined cellular components confers the ability to discriminate among closely related oligosaccharide structures. This is consistent with a model in which only glycopeptides bearing terminal Gal or GalNAc residues that fall within a restricted spatial relationship can induce a conformational alteration in the receptor which is required for uptake to occur. The endocytosis of a number of glycoproteins such as human asialo-ceruloplasmin can be accounted for by the presence of a single, complex oligosaccharide with the appropriate structure.
D000116:Acetylgalactosamine / Q000378:metabolism*; D000818:Animals; D000936:Antigen-Antibody Complex; D050260:Carbohydrate Metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002570:Ceruloplasmin / Q000378:metabolism; D000070821:Discoidins; D004705:Endocytosis; D005688:Galactosamine / Q000031:analogs & derivatives*; D005690:Galactose / Q000378:metabolism*; D006020:Glycopeptides / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D037102:Lectins; D008099:Liver / Q000378:metabolism*; D009844:Oligosaccharides / Q000378:metabolism; D015800:Protozoan Proteins; D051381:Rats
D000936:Antigen-Antibody Complex; D002352:Carrier Proteins; D000070821:Discoidins; D006020:Glycopeptides; D006023:Glycoproteins; D037102:Lectins; D009844:Oligosaccharides; D015800:Protozoan Proteins; D005688:Galactosamine; D002570:Ceruloplasmin; D000116:Acetylgalactosamine; D005690:Galactose