Monensin Blocks the Transport of Diphtheria Toxin to the Cell Cytoplasm

Lysosomotropic amines are believed to inhibit the transport of diphtheria toxin to the cell cytoplasm by raising the pH within intracellular vesicles. If so, then other drugs that dissipate intracellular proton gradients should have a similar effect on toxin transport. We found that monensin, a prot...

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Bibliographic Details
Published in:The Journal of cell biology 1982-04, Vol.93 (1), p.57-62
Main Authors: Marnell, Mary H., Stookey, Margaret, Draper, Rockford K.
Format: Article
Language:English
Subjects:
Animals
Antitoxins
Biological Transport - drug effects
Cell Line
Cell membranes
Cells
Cercopithecus aethiops
Chlorides
Concanavalin A - pharmacology
Cytoplasm
Diphtheria
Diphtheria Toxin - metabolism
Diphtheria Toxin - pharmacology
Endocytosis - drug effects
Furans - pharmacology
Kidney
Kinetics
Monensin - pharmacology
Protein synthesis
Protons
Quaternary ammonium compounds
Toxins
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Summary:Lysosomotropic amines are believed to inhibit the transport of diphtheria toxin to the cell cytoplasm by raising the pH within intracellular vesicles. If so, then other drugs that dissipate intracellular proton gradients should have a similar effect on toxin transport. We found that monensin, a proton ionophore unrelated to lysosomotropic amines, is a potent inhibitor of the cytotoxic effect of diphtheria toxin. Monensin appears to block the escape of endocytosed toxin from a vesicle to the cytoplasm. Monensin fails to protect cells from the effects of diphtheria toxin that is bound to the cell surface and exposed to acidic medium, suggesting that the step normally blocked by the drug is circumvented under these conditions. The inhibition of toxin transport caused by monensin could not be relieved when monensin was replaced by ammonium chloride, nor when ammonium chloride was again replaced by monensin. This suggests that both drugs block the same step of toxin transport. The effect of monensin on the transport of diphtheria toxin to the cytoplasm is consistent with the proposal that the toxin is endocytosed and then, in response to an acidic environment, penetrates through the membrane of an intracellular vesicle to reach the cytoplasm.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.93.1.57