The asialoglycoprotein receptor clears glycoconjugates terminating with sialic acid alpha 2,6GalNAc.
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.
Park
Eric I
EI
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Mi
Yiling
Y
Unverzagt
Carlo
C
Gabius
Hans-Joachim
HJ
Baenziger
Jacques U
JU
D000116:Acetylgalactosamine / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D001667:Binding, Competitive / Q000235:genetics; D002240:Carbohydrate Sequence; D005690:Galactose / Q000097:blood / Q000493:pharmacokinetics; D006001:Glycoconjugates / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008024:Ligands; D008657:Metabolic Clearance Rate / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary; D051381:Rats; D013045:Species Specificity; D013379:Substrate Specificity
D037263:Asialoglycoprotein Receptor; D006001:Glycoconjugates; D008024:Ligands; D019158:N-Acetylneuraminic Acid; D000116:Acetylgalactosamine; D005690:Galactose