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PMID: 6888380 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

Binding and uptake of diphtheria toxin by toxin-resistant Chinese hamster ovary and mouse cells.

Molecular and cellular biology ·Vol. 3 ·No. 7 ·1983-07-00 ·Pages 1283-94

Didsbury JR, Moehring JM, Moehring TJ

Abstract

We investigated two phenotypically distinct types of diphtheria toxin-resistant mutants of Chinese hamster cells and compared their resistance with that of naturally resistant mouse cells. All are resistant due to a defect in the process of internalization and delivery of toxin to its target in the cytosol, elongation factor 2. By cell hybridization studies, analysis of cross-resistance, and determination of specific binding sites for 125I-labeled diphtheria toxin, we showed that these cell strains fall into two distinct complementation groups. The Dipr group encompasses Chinese hamster strains that are resistant only to diphtheria toxin, as well as mouse LM cells. These strains possess a normal complement of high-affinity binding sites for diphtheria toxin, but these receptors are unable to deliver active toxin fragment A to the cytosol. Cells of the DPVr group have a broader spectrum of resistance, including Pseudomonas exotoxin A and several enveloped viruses as well as diphtheria toxin. In these studies, which investigate the resistance of these cells to diphtheria toxin, we demonstrate that they possess a reduced number of specific binding sites for this toxin and behave, phenotypically, like cells treated with the proton ionophore monensin. Their resistance is related to a defect in a mechanism required for release of active toxin from the endocytic vesicle.

MeSH Terms
Ammonium Chloride/pharmacology Animals Binding Sites Biological Transport, Active Cells, Cultured Cricetinae Cricetulus Diphtheria Toxin/metabolism,toxicity Drug Resistance Female Heparin-binding EGF-like Growth Factor Intercellular Signaling Peptides and Proteins Mice Monensin/pharmacology Mutation Ovary Receptors, Cell Surface Receptors, Cholinergic/metabolism
Chemicals
Diphtheria Toxin Hbegf protein, mouse Heparin-binding EGF-like Growth Factor Intercellular Signaling Peptides and Proteins Receptors, Cell Surface Receptors, Cholinergic Ammonium Chloride Monensin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Didsbury J R
Moehring J M
Moehring T J
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51 references, click to expand
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.3.7.1283-1294.1983
Published
1983-07-00
Pages
1283-94
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC370119
Subset
IM
Grants
NIAID NIH HHS · AI-09100 · United States
External Links
PubMed source DOI: 10.1128/mcb.3.7.1283-1294.1983 PMC Full Text View journal details
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