Ricin intoxicates End4 mutants that have an aberrant Golgi complex.
Ricin is a protein toxin that arrests protein synthesis in mammalian cells by catalytically inactivating ribosomes. To interact with ribosomes, the A chain of the toxin must enter the cytosol. Entry involves receptor-mediated endocytosis and penetration of the toxin through an intracellular membrane, but the identity of the compartment where penetration occurs is unknown. It has been suggested that the A chain penetrates from the endoplasmic reticulum, implying the existence of a pathway from endosomes to the endoplasmic reticulum, perhaps via, retrograde transport through the Golgi. (For a recent review, see Pelham, H. R. B., Roberts, L. M., and Lord, J. M. (1992) Trends Cell Biol. 2, 183-185.) To investigate the role of the Golgi in the intoxication process of ricin, we studied the effect of ricin on mutants of the End4 complementation group of Chinese hamster ovary cells. End4 mutants express a temperature-sensitive block in secretion that is correlated with the disappearance of the Golgi stacks at the level of fluorescence microscopy. We found that End4 cells and wild-type cells were equally sensitive to ricin at the restrictive temperature, although the minimum lag before inhibition of protein synthesis was longer in the mutant cells. The simplest interpretation of these data is that ricin does not pass through the cis, medial, or trans stacks of the Golgi en route to the cytosol.
Bau
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Molecular and Cell Biology Program, University of Texas at Dallas, Richardson 75083.
Draper
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D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D020126:Brefeldin A; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D006224:Cricetinae; D003517:Cyclopentanes / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006056:Golgi Apparatus / Q000187:drug effects / Q000648:ultrastructure*; D007700:Kinetics; D016296:Mutagenesis; D011500:Protein Synthesis Inhibitors / Q000633:toxicity*; D012276:Ricin / Q000378:metabolism / Q000633:toxicity*; D013696:Temperature
D000900:Anti-Bacterial Agents; D003517:Cyclopentanes; D011500:Protein Synthesis Inhibitors; D020126:Brefeldin A; D012276:Ricin