Functional galactosyl receptors on isolated rat hepatocytes are hetero-oligomers

Several lines of indirect evidence have supported the conclusion that rat hepatic asialoglycoprotein (or galactosyl; Gal) receptors are hetero-oligomeric. In the present study more direct evidence was obtained using specific antibodies. The Gal receptor contains three different subunits; RHL 1, RHL 2 and RHL 3. Polyclonal antisera that specifically recognize either RHL 1 or RHL 2/3 subunits (Halberg et al., J. Biol. Chem. 262, 9828, 1987) were tested for their ability to interfere with the specific binding of asialo-orosomucoid to intact rat hepatocytes. The different antisera used all completely inhibited specific ligand binding to the receptor. These results indicate that functional Gal receptors on the cell surface are composed of multiple types of subunits. In addition, no evidence was found to suggest that the two previously described functionally distinct receptor populations in hepatocytes can be explained by these receptor populations containing different RHL subunits. We conclude that all receptors on the cell surface are composed of multiple subunits.