ISOLATION OF THE 4-GALNAC-BETA-1,4GLCNAC-BETA-1,2MAN-ALPHA-SPECIFIC RECEPTOR FROM RAT-LIVER

Glycoproteins, such as the glycoprotein hormone lutropin (LH), bear ol igosaccharides terminating with the sequence SO4-4GalNAc beta 1,4GlcNA c beta 1,2Man alpha (S4GGnM) and are rapidly removed from the circulat ion by a receptor present in hepatic endothelial cells and Kupffer cel ls, Rapid removal from the circulation is essential for attaining maxi mal hormone activity in vivo. We have isolated a protein from rat live r which has the properties expected for the S4GGnM-specific receptor ( S4GGnM-R). The S4GGnM-R is closely related to the macrophage mannose r eceptor (Man-R) both antigenically and structurally. At least 12 pepti des prepared from the S4GGnM-R have amino acid sequences that are iden tical to those of the Man-R, Nonetheless, the ligand binding propertie s of the S4GGnM-R and the Man-R differ in a number of respects, The S4 GGnM-R binds to immobilized LH but not to immobilized mannose, whereas the Man-R binds to immobilized mannose but not to immobilized LH, Whe n analyzed using a binding assay that precipitates receptor ligand com plexes with polyethylene glycol, the S4GGnM-R is able to bind S4GGnM-b ovine serum albumin (S4GGnM-BSA) conjugates gates 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 enh ance 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 accoun t for clearance of glycoproteins bearing oligosaccharides terminating with S4GGnM and glycoproteins bearing oligosaccharides terminating wit h either mannose, fucose, or N-acetylglucosamine.