Hepatic receptor that specifically binds oligosaccharides containing fucosyl α1→3 N -acetylglucosamine linkages

Abstract

Evidence is presented suggesting that hepatocytes contain a receptor that binds glycoproteins specifically through fucose in al-..3 linkage to N-acetylglucosamine. Human After the initial observations of Ashwell and coworkers (1, 2) that mammalian hepatocytes contain a protein that specifically binds asialoglycoproteins through exposed galactose residues, several other animal binding proteins were reported. A (3-galactoside binding protein has been described from calf heart and lung (3), chick embryo thigh muscle (4), and the electric organ of Electrophorus electricus (5), but they have properties that differ somewhat from the hepatocyte protein and perhaps from one another. Avian liver also contains a protein that binds glycoproteins with exposed N-acetylglucosamine (6), and considerable evidence has been reported for mannose-specific binding proteins (7).This report provides evidence suggesting the presence of a receptor in hepatocytes that specifically binds oligosaccharides in glycoproteins through a fucosyl al-3 N-acetylglucosamine group. These studies were prompted by the observations that human lactoferrin (Lf) was rapidly cleared from the circulation when injected intravenously in rats and mice, and that over 90% of the injected protein was recovered in hepatocytes.The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement " in accordance with 18 U. S. C. §1734 solely to indicate this fact.Much is known about Lf structure although its biological role is obscure (8). Lf, like serotransferrin (Tf), has two iron-binding sites, and iron binding is dependent on bicarbonate (9). Its amino acid sequence is homologous with that of Tf (10, 11) and ovotransferrin (11) and it contains two oligosaccharide chains, which are structurally similar to those of serotransferrin ( Fig. 1), except that additional fucose residues are in a1->3 linkage with the N-acetylglucosamine residues adjacent to galactose and those chains containing fucose are devoid of sialic acid (11, 12, and unpublished observations

Structural Features of the Carbohydrate Units of Plasma Glycoproteins

“…Recently a fucose-binding from the present study, those for rat liver, kidney and brain from [lo], those for human erythrocytes from [12]. The hatched areas in erythrocytes refer to the portion found as poly(glycosy1)peptides [12] protein specific for the sequence Gal(/31+4)[Fuc-(a1 -+ 3)IGlcNAc has been described [5]. The amount of fucose was found to be very low in plasma glycoproteins and it appeared to be bound by other types of linkages, since almost no 3 or 3,4-disubstituted N-acetylglucosamine residues were found to be present.…”

Enzymatic basis for a lectin-resistant phenotype: increase in a fucosyltransferase in mouse melanoma cells.

“…Fucose has been shown to be a part of antigenic determinants, including the so called X-antigen (34), and may be also be part of the receptor for the macrophage migration inhibitory factor (35) . A specific hepatic uptake system for the a l ---+ 3 linked fucose has also been described (36) . One of the WGARLots cell lines has been shown to differ from the parent cells with respect to cell adhesion and metastasis (11) .…”

L-Fucose-terminated glycoconjugates are recognized by pinocytosis receptors on macrophages.

“…Cells (5 x 105) in 0.1 ml were layered over oil (4 parts silicon oil plus I part mineral oil) in Microfuge (Beckman) tubes. The interaction of ligand with cells was terminated by sedimentation for 30 (6). Previous work has shown that the rate at which -glucuronidase is cleared from plasma is sharply decreased by the simultaneous administration of mannose-or Nacetylglucosamine-terminated glycoproteins (6,8).…”