Antibody-induced receptor loss. Different fates for asialoglycoproteins and the asialoglycoprotein receptor in HepG2 cells

A. L. Schwartz, A. Ciechanover, S. Merritt, A. Turkewitz

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The human asialoglycoprotein receptor (ASGP-R) is a membrane glycoprotein which participates in receptor-mediated endocytosis and delivery of its ligands to lysosomes for degradation. In order to examine the pathways and mechanisms responsible for the turnover and degradation of the ASGP-R we have followed the fate of the ASGP-R in HepG2 cells during exposure to anti-receptor antibody as well as inhibitors of lysosomal processing and receptor recycling. Incubation of cells at 37°C with anti-ASGP-R antibody results in the rapid (t( 1/2 ) 30 min) loss of mature 46,000-Da ASGP-R (control, t( 1/2 ) 20 h). This process requires whole IgG, since Fab fragments do not induce loss of receptor. Furthermore, this antibody-induced loss is specific, since incubation with antibody to the transferrin receptor does not alter cellular ASGP-R content. Of note, weak bases (e.g. primaquine) abrogate this antibody-induced loss of ASGP-R. Inhibitors of lysosomal proteases (EC64 and leupeptin) do not alter this antibody-mediated loss. Furthermore, this effect occurs at 18°C, a temperature at which delivery of ligand to the lysosome is blocked. Thus, the present observations suggest a unique pathway for antibody-induced ASGP-R loss which is distinct from the pathway of lysosomal delivery of ligand.

Original languageEnglish
Pages (from-to)15525-15232
Number of pages294
JournalJournal of Biological Chemistry
Volume261
Issue number32
StatePublished - Jan 1 1986

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