Shiga toxin produced by Shigella dysenteriae acts primarily on the vascular endothelial cells lining small blood vessels. After binding to its target cells through a glycolipid receptor, the toxin is partly endocytosed from clathrin-coated pits and transported through the Golgi and the endoplasmic reticulum to the cytosol where, by inhibiting ribosomes, it kills the cell. On , Kirsten Sandvig and colleagues investigate the intracellular transport of Shiga toxin and show that this requires dynamin and clathrin. By using HeLa dynK44A cells, which express mutant dynamin in the absence of tetracycline, the authors show that functional dynamin is required for Shiga toxin transport both in untreated cells and in cells treated with butyric acid, which sensitizes cells to Shiga toxin by increasing its transport to the Golgi. Additional experiments using BHK cells that inducibly express antisense RNA directed against the clathrin heavy chain indicate that functional clathrin is more important for endosome-to-Golgi Shiga transport in butyric-acid-sensitized cells than in untreated cells. Thus, the exact intracellular transport mechanism used depends on the cell's sensitivity to the toxin.
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