The macrophage/endothelial cell mannose receptor cDNA encodes a protein that binds oligosaccharides terminating with SO 4 -4-GalNAcβ1,4GlcNAcβ or Man at independent sites

• Published in: Proceedings of the National Academy of Sciences - PNAS 1997-10, Vol.94 (21), p.11256-11261
• Main Authors: Fiete, Dorothy, Beranek, Mary C., Baenziger, Jacques U.
• Format: Article
• Language: English
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.21.11256

Lutropin (LH) and other glycoproteins bearing oligosaccharides with the terminal sequence SO 4 -4-GalNAcβ1,4GlcNAcβ1,4Man- (S4GGnM) are rapidly removed from the circulation by an S4GGnM-specific receptor (S4GGnM-R) expressed at the surface of hepatic endothelial cells. The S4GGnM-R isolated from rat liver is closely related to the macrophage mannose-specific receptor (Man-R) isolated from rat lung both antigenically and structurally. The S4GGnM-R and Man-R isolated from these tissues nonetheless differ in their ability to bind ligands bearing terminal GalNAc-4-SO 4 or Man. In this paper, we have explored the structural relationship between the Man-R and the S4GGnM-R by examining the properties of the recombinant Man-R in the form of a transmembrane protein and a soluble chimeric fusion protein in which the transmembrane and cytosolic domains have been replaced by the Fc region of human IgG1. Like the S4GGnM-R isolated from liver, the chimeric fusion protein is able to bind ligands terminating with GalNAc-4-SO 4 and Man at independent sites. When expressed in CHO cells the recombinant Man-R is able to mediate the uptake of ligands bearing either terminal GalNAc-4-SO 4 or terminal Man. We propose that the Man-R be renamed the Man/S4GGnM receptor on the basis of its multiple and independent specificities.