Monensin inhibits intracellular dissociation of asialoglycoproteins from their receptor

J. Harford, Allan W. Wolkoff, G. Ashwell, R. D. Klausner

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Treatment of short-term monolayer cultures of rat hepatocytes with the proton ionophore, monensin, abolishes asialoglycoprotein degradation, despite little effect of the drug on either surface binding of ligand or internalization of prebound ligand. Centrifuging cell homogenates on Percoll density gradients indicates that, as a result of monensin treatment, ligand does not enter lysosomes but sediments instead in a lower density subcellular fraction that is likely an endocytic vesicle. Analyzing the degree of receptor association of intracellular ligand revealed that monensin prevents the dissociation of the receptor-ligand complex that normally occurs subsequent to endocytosis. The weak base, chloroquine, also blocks this intracellular dissociation. Evidence from sequential substitution experiments is presented, indicating that monensin and chloroquine act at the same point in the sequence of events leading to ligand dissociation. These data are discussed in terms of a pH-mediated dissociation of the receptor-ligand complex within a prelysosomal endocytic vesicle.

Original languageEnglish (US)
Pages (from-to)1824-1828
Number of pages5
JournalJournal of Cell Biology
Volume96
Issue number6
StatePublished - 1983
Externally publishedYes

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Asialoglycoprotein Receptor
Monensin
Ligands
Transport Vesicles
Chloroquine
Proton Ionophores
Asialoglycoproteins
Subcellular Fractions
Endocytosis
Lysosomes
Hepatocytes

ASJC Scopus subject areas

  • Cell Biology

Cite this

Monensin inhibits intracellular dissociation of asialoglycoproteins from their receptor. / Harford, J.; Wolkoff, Allan W.; Ashwell, G.; Klausner, R. D.

In: Journal of Cell Biology, Vol. 96, No. 6, 1983, p. 1824-1828.

Research output: Contribution to journalArticle

Harford, J. ; Wolkoff, Allan W. ; Ashwell, G. ; Klausner, R. D. / Monensin inhibits intracellular dissociation of asialoglycoproteins from their receptor. In: Journal of Cell Biology. 1983 ; Vol. 96, No. 6. pp. 1824-1828.
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