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The asialoglycoprotein receptor clears glycoconjugates terminating with sialic acid alpha 2,6GalNAc.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2005 Nov 22; Vol. 102 (47), pp. 17125-9. Date of Electronic Publication: 2005 Nov 14. - Publication Year :
- 2005
-
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.
- Subjects :
- Acetylgalactosamine blood
Acetylgalactosamine chemistry
Animals
Asialoglycoprotein Receptor deficiency
Asialoglycoprotein Receptor genetics
Binding, Competitive genetics
Carbohydrate Sequence
Galactose blood
Galactose pharmacokinetics
Glycoconjugates blood
Glycoconjugates chemistry
Ligands
Metabolic Clearance Rate genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular Sequence Data
N-Acetylneuraminic Acid blood
N-Acetylneuraminic Acid chemistry
Protein Binding genetics
Protein Structure, Tertiary
Rats
Species Specificity
Substrate Specificity
Acetylgalactosamine pharmacokinetics
Asialoglycoprotein Receptor blood
Glycoconjugates pharmacokinetics
N-Acetylneuraminic Acid pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 102
- Issue :
- 47
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 16286643
- Full Text :
- https://doi.org/10.1073/pnas.0508537102