Cytolethal Distending Toxin: A Unique Variation on the AB Toxin Paradigm

Figure 5

Comparison of cell intoxication pathways of representative AB toxins. Based on the available information, the toxins shown may or may not bind to lipid rafts and enter the cell by either a clathrin-dependent or independent receptor-mediated endocytosis. Anthrax, botulinum, and tetanus toxins are not translocated to the Golgi apparatus and endoplasmic reticulum (ER) but enter the cytosol from early endosomes. Additional details are provided in the text. Unique features of Cdt intoxication are (i) endocytosis of CdtB and CdtC rather than the intact holotoxin, (ii) dynamin II participation in early endosome formation, (iii) translocation of CdtB by a non-ER-associated degradation (ERAD) pathway, and (iv) translocation of CdtB across the nuclear membrane via a nuclear localization signal (NLS).