In control cells, GPP130 cycles from the Golgi to endosomes and back. After internalization into endosomes, Shiga toxin binds GPP130 and is sorted into endosome membrane tubules that break off and deliver the toxin to the Golgi. From there it moves to the ER and then the cytoplasm causing cell death. In manganese treated cells, GPP130 moves to lysosomes and is degraded. After internalization into endosomes, Shiga toxin stays in the larger part of the endosome because of the absence of GPP130. As a consequence, Shiga toxin moves to lysosomes (the default pathway for internalized content) where it is degraded.
Credit: Carnegie Mellon University
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