A hepatic reticuloendothelial cell receptor specific for SO4-4GalNAc beta 1,4GlcNAc beta 1,2Man alpha that mediates rapid clearance of lutropin.
We have identified a receptor in hepatic endothelial and Kupffer cells that binds oligosaccharides terminating with the sequence SO4-4GalNAc beta 1,4GlcNAc beta 1,2-Man alpha (S4GGnM). This receptor can account for the rapid removal of the glycoprotein hormone lutropin, which bears unique Asn-linked oligosaccharides terminating in S4GGnM, from the circulation. Hepatic endothelial cells express 579,000 S4GGnM receptors at their surface and bind lutropin with an apparent Kd of 1.63 x 10(-7) M. Bound ligand is rapidly internalized. Binding does not require divalent cations, is reversed by incubation at pH 5.0 or below, and is inhibited by fucoidin but not by hyaluronate, heparin, chondroitin sulfate, or dextran sulfate. We propose that the S4GGnM-specific receptor represents a major mechanism for clearance of certain sulfated glycoproteins from the blood, including members of the glycoprotein hormone family.
Fiete
D
D
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
Srivastava
V
V
Hindsgaul
O
O
Baenziger
J U
JU
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002240:Carbohydrate Sequence; D004705:Endocytosis; D004730:Endothelium, Vascular / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D066298:In Vitro Techniques; D007728:Kupffer Cells / Q000378:metabolism; D008024:Ligands; D008099:Liver / Q000378:metabolism*; D007986:Luteinizing Hormone / Q000737:chemistry / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D008969:Molecular Sequence Data; D012157:Mononuclear Phagocyte System / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013431:Sulfates / Q000737:chemistry
D006023:Glycoproteins; D008024:Ligands; D011956:Receptors, Cell Surface; D013431:Sulfates; D007986:Luteinizing Hormone