In early endosomes, Shiga toxin (green) is sorted into membrane tubules, which pinch off and move to the Golgi apparatus. The membrane left behind, marked by epidermal growth factor (red), eventually fuses with lysosomes and its contents are destroyed. Sorting into the Golgi-destined membrane tubules depends on Shiga toxin binding to GPP130. Manganese protects cells by down-regulating GPP130. Without GPP130 to bind, Shiga toxin does not enter the endosomal membrane tubules and, as a consequence, it is degraded in lysosomes.