Figure 1. Vesicular trafficking schemes.

Following clathrin-independent endocytosis, the cytotoxic fractions of ricin and Shiga –like toxin (SLTx) traffic to the ER via early endosmes (EE), the trans-Golgi network (TGN) and the Golgi apparatus to the endoplasmic reticulum (ER), where the ricin subunits RTA and RTB are reductively separated. It is assumed that SLTxA chain is also separated from its B chain pentamer (SLTxB) in the ER. The toxic RTA and SLTxA chains are thought to co-opt ERAD mechanisms to dislocate from the ER to the cytosol, where they are refolded to recover toxic catalytic activity (ribosome modification). Diphtheria toxin (DTx) is endocytosed in a clathrin-dependent manner (hatched area) and enters the cytosol from acidified endosomes. In the cytosol it is reduced, releasing the A chain (DTxA) which inactivates elongation factor 2. Blue boxes, areas/processes affected by ES_I: lower box, previously identified targets; upper box, this study. PM, plasma membrane.