Fig. 11. Model of the cytotoxic internalization of ribonucleases. RNase A and ONC bind to the cell surface and are internalized by dynamin-independent endocytosis. Like diptheria toxin, both ribonucleases probably reach the cytosol by translocation from an endosome. Unlike diphtheria toxin, the low pH of acidic endosomes is not a prerequisite for the translocation of RNase A and ONC to the cytosol. The entry of ONC to the Golgi is inefficient for cytotoxicity. Unlike ricin and Shiga toxin, both ribonucleases reach the cytosol by translocation from a pre-ER compartment.