The asialoglycoprotein receptor clears glycoconjugates terminating with sialic acid alpha 2,6GalNAc. Proceedings of the National Academy of Sciences of the United States of America. [Proc Natl Acad Sci U S A] Journal article | | Title | The asialoglycoprotein receptor clears glycoconjugates terminating with sialic acid alpha 2,6GalNAc. | | Author(s) | Park EI, Mi Y, Unverzagt C, Gabius HJ, Baenziger JU | | Institution | Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA. | | Source | Proc Natl Acad Sci U S A 2005 Nov 22; 102(47):17125-9. | | MeSH | Acetylgalactosamine
Animals
Asialoglycoprotein Receptor
Binding, Competitive
Carbohydrate Sequence
Galactose
Glycoconjugates
Ligands
Metabolic Clearance Rate
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular Sequence Data
N-Acetylneuraminic Acid
Protein Binding
Protein Structure, Tertiary
Rats
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Species Specificity
Substrate Specificity
| | Abstract | Endogenous ligands have not, to date, been identified for the asialoglycoprotein receptor (ASGP-R), which is abundantly expressed by parenchymal cells in the liver of mammals. On the basis of the rapid clearance of BSA bearing multiple chemically coupled sialic acid (Sia)alpha2,6GalNAcbeta1,4GlcNAcbeta1,2Man tetrasaccharides (SiaGGnM-BSA) from the circulation, and the ability of the ASGP-R hepatic lectin-1 subunit to bind SiaGGnM-BSA, we previously proposed that glycoproteins modified with structures terminating with Siaalpha2,6GalNAc may represent previously unrecognized examples of endogenous ligands for this receptor. Here, we have taken a genetic approach using wild-type and ASGP-R-deficient mice to determine that the ASGP-R in vivo does indeed account for the rapid clearance of glycoconjugates terminating with Siaalpha2,6GalNAc. We have also determined that the ASGP-R is able to bind core-substituted oligosaccharides with the terminal sequence Siaalpha2,6Galbeta1,4GlcNAc but not those with the terminal Siaalpha2,3Galbeta1,4GlcNAc. We propose that glycoproteins bearing terminals Siaalpha2,6GalNAc and Siaalpha2,6Gal are endogenous ligands for the ASGP-R, and that the ASGP-R helps to regulate the relative concentration of serum glycoproteins bearing alpha2,6-linked Sia. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 16286643 |
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