title: The major subunit of the asialoglycoprotein receptor is expressed on the hepatocellular surface in mice lacking the minor receptor subunit.
abstract: The mammalian asialoglycoprotein receptor (ASGPR) is located on the sinusoidal membrane of hepatocytes where it binds and endocytoses galactose-terminated glycoproteins (asialoglycoproteins). ASGPR is composed of two highly homologous subunits, termed hepatic lectin 1 and 2. Despite numerous studies the contribution of both subunits to biosynthesis and functional activity of ASGPR in vivo has remained controversial. Mice lacking the murine hepatic lectin (MHL)-2 subunit are viable and fertile without obvious phenotypic abnormalities. In the absence of MHL-2, knockout mice express MHL-1 protein at reduced levels. Here, we examine the intracellular fate and function of this remaining subunit. The results show that MHL-1 reaches the hepatocellular surface in knockout mice but is unable to effectively remove any one of three different radiolabeled ligands within 30 min. A small but detectable residual ligand clearance in knockout mice at 4 h is apparently not mediated by remaining MHL-1. Serum concentrations of galactose-terminating glycoproteins are not elevated in these ASGPR-deficient mice. However, competitive in vitro degradation experiments suggest that other endogenous ASGPR ligands, the nature of which remain to be determined, accumulate in serum of knockout animals.
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas Texas 75235, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Braun
authors.forename: T E
authors.initials: TE
authors.lastname: Willnow
authors.forename: S
authors.initials: S
authors.lastname: Ishibashi
authors.forename: G
authors.initials: G
authors.lastname: Ashwell
authors.forename: J
authors.initials: J
authors.lastname: Herz
mesh_terms: D000818:Animals; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D037102:Lectins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*
chemical_list: D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D037102:Lectins; D011956:Receptors, Cell Surface