The Major Subunit of the Asialoglycoprotein Receptor Is Expressed on the Hepatocellular Surface in Mice Lacking the Minor Receptor Subunit

• Published in: The Journal of biological chemistry Vol. 271; no. 35; pp. 21160 - 21166
• Main Authors: Braun, J R, Willnow, T E, Ishibashi, S, Ashwell, G, Herz, J
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 30.08.1996
• Subjects: Animals; Asialoglycoprotein Receptor; Asialoglycoproteins - metabolism; Cell Membrane - metabolism; Lectins - genetics; Lectins - metabolism; Liver - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Phenotype; Radioligand Assay; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.271.35.21160

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.