The oligosaccharides on soluble and membrane glycoproteins exhibit tremendous structural diversity, suggesting they encode highly specific information. For this to be the case there must exist: l) Unique oligosaccharide structures, 2) Highly specific glycosyltransferases, and 3) Receptors capable of recognizing these structures and utilizing their unique information. Biologic functions making use of information encoded in oligosaccharides are likely to be manifest primarily in multicellular organisms and include such phenomena as cell:cell recognition, cell:matrix recognition, and both intra- and extra-cellular trafficking of glycoproteins. The challenge has been to identify systems which utilize the structural information encoded in oligosaccharides for a biologic purpose. We have identified a major new carbohydrate-specific receptor system in liver which regulates the circulatory half life and, thereby, the biologic activity of the glycoprotein hormone lutropin and other glycoproteins bearing terminal SO4-4GalNAc-beta, 14GlcNAc-beta1, 2Man- alpha (S4GGnM) on their oligosaccharides. The synthesis of S4GGnM-terminal structures is highly regulated and they are found on only a limited number of glycoproteins. Hepatic endothelial cell express >500,000 S4GGnM-binding sites/cell at their surface. The S4OGnM-receptor has been isolated from rat liver and will be extensively characterized using approaches we have developed for other carbohydrate-specific systems. The properties of the receptor will be defined in isolated hepatic endothelial cells. The primary structure will be determined by cDNA analysis. Proteolytic fragmentation and mutagenesis will be used to define the regions involved in ligand binding and targeting. Additional potential functions will be established by using the receptor to identify other glycoproteins bearing S4GGnM-terminal structures. Cells expressing the receptor in other tissues will be identified and characterized to establish if the receptor is part of a multigene family. Immunolocalization and in situ hybridization will be used to examine the regulation of S4GGnM-receptor expression during fetal development, pregnancy, and gain of sexual maturity in newborn rats. Since many glycoproteins including membrane glycoproteins on normal and malignant cells, surface glycoproteins on viruses, growth factor precursors, coagulation factors, complement components, and hormones may interact with the receptor system it has tremendous potential relevance to both pathologic and normal states.

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National Cancer Institute (NCI)
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Washington University
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Saint Louis
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Mi, Yiling; Coonce, Marcy; Fiete, Dorothy et al. (2016) Functional Consequences of Mannose and Asialoglycoprotein Receptor Ablation. J Biol Chem 291:18700-17
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