Rapid clearance of sialylated glycoproteins by the asialoglycoprotein receptor.
The asialoglycoprotein-receptor (ASGP-R) located on liver parenchymal cells was originally identified and characterized on the basis of its ability to bind glycoproteins bearing terminal galactose (Gal) or N-acetylgalactosamine (GalNAc); however, endogenous ligands for the ASGP-R have not to date been definitively identified. We have determined that the rat ASGP-R specifically binds oligosaccharides terminating with the sequence Siaalpha2,6GalNAcbeta1,4GlcNAcbeta1,2Man. Bovine serum albumin chemically modified with 10-15 tetrasaccharides with the sequence Siaalpha2,6GalNAcbeta1,4GlcNAcbeta1,2Man is cleared from the blood of the rat with a half-life of <1 min by a receptor located in the liver. We have isolated the receptor and identified it as the ASGP-R. Furthermore, we have determined that subunit 1 of the ASGP-R accounts for the binding of terminal Siaalpha2,6GalNAcbeta. Based on the newly defined specificity of the rat ASGP-R we hypothesize that glycoproteins bearing structures that are selectively modified with terminal Siaalpha2,6GalNAcbeta and are released into the blood may be endogenous ligands for the rat ASGP-R.
Park
Eric I
EI
Department of Pathology, School of Medicine, Washington University, St. Louis, Missouri 63110, USA.
Manzella
Stephen M
SM
Baenziger
Jacques U
JU
D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000378:metabolism*; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D006207:Half-Life; D008024:Ligands; D008099:Liver / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D012795:Sialoglycoproteins / Q000378:metabolism*
D037263:Asialoglycoprotein Receptor; D008024:Ligands; D012795:Sialoglycoproteins; D002118:Calcium