Retrograde transport of Shiga toxin 1 in human renal tubular epithelial cells

: To displays its cytotoxicity by initiating RNA cleavage, Stx1 is required to be transported from endosomes to the endoplasmic reticulum, where the translocation of the A-subunit to the cytosol occurs. In the case of established cell lines, it is reported that a large proportion of the internalized Stx is transported to lysosomes for degradation and only a fraction of the toxin molecules can reach to the cytosol. By using primary culture cells, however, we observed that Stx1 is effectively delivered to the cytosol in normal human renal tubular epithelial cells. Investigation of retrograde transport mechanism of Stx should provide insights into the analysis of Stx-mediated cell damage and lead to improvements in therapeutic approaches for diseases caused by Stx.