Fig. 5. Rab proteins involved in retrograde transport from endosomes to the ER. Toxins enter cells either by clathrin-independent or clathrin-dependent endocytosis. Initial pathways of uptake converge on early endosomes, except for the caveosome pathway which apparently bypasses the typical endosomal system in transporting material to the ER. One pathway from early endosomes to the TGN is via late endosomes that use Rab7 and Rab9 in sequential steps. Another pathway to the TGN is via recycling endosomes and involves Rab6A' and Rab11 in different steps. Rab6A' may also participate in the direct transport of material from early endosomes to the TGN. Two pathways are proposed to transport material from the TGN-Golgi complex to the ER, the COPI-dependent pathway that is regulated by Rab6A and the COPI-independent pathway that is not believed to require Rab6A.