Isolation of the SO4-4-GalNAcbeta1,4GlcNAcbeta1,2Manalpha-specific receptor from rat liver.
Glycoproteins, such as the glycoprotein hormone lutropin (LH), bear oligosaccharides terminating with the sequence SO4-4GalNAcbeta1, 4GlcNAcbeta1,2Manalpha (S4GGnM) and are rapidly removed from the circulation by a receptor present in hepatic endothelial cells and Kupffer cells. Rapid removal from the circulation is essential for attaining maximal hormone activity in vivo. We have isolated a protein from rat liver which has the properties expected for the S4GGnM-specific receptor (S4GGnM-R). The S4GGnM-R is closely related to the macrophage mannose receptor (Man-R) both antigenically and structurally. At least 12 peptides prepared from the S4GGnM-R have amino acid sequences that are identical to those of the Man-R. Nonetheless, the ligand binding properties of the S4GGnM-R and the Man-R differ in a number of respects. The S4GGnM-R binds to immobilized LH but not to immobilized mannose, whereas the Man-R binds to immobilized mannose but not to immobilized LH. When analyzed using a binding assay that precipitates receptor ligand complexes with polyethylene glycol, the S4GGnM-R is able to bind S4GGnM-bovine serum albumin (S4GGnM-BSA) conjugates whereas the Man-R is not. In contrast both the S4GGnM-R and the Man-R are able to bind Man-BSA. Monosaccharides that inhibit binding of Man-BSA by the Man-R enhance binding by the S4GGnM-R. Oligosaccharides terminating with S4GGnM and those terminating with Man are bound at independent sites on the S4GGnM-R. The S4GGnM-R present in hepatic endothelial cells may account for clearance of glycoproteins bearing oligosaccharides terminating with S4GGnM and glycoproteins bearing oligosaccharides terminating with either mannose, fucose, or N-acetylglucosamine.
Fiete
D
D
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Baenziger
J U
JU
D000595:Amino Acid Sequence; D000818:Animals; D002240:Carbohydrate Sequence; D002846:Chromatography, Affinity; D006023:Glycoproteins; D007202:Indicators and Reagents; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009844:Oligosaccharides / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry; D010449:Peptide Mapping; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism*
D006023:Glycoproteins; D007202:Indicators and Reagents; D009844:Oligosaccharides; D010446:Peptide Fragments; D011956:Receptors, Cell Surface