Endocytosis and retrograde transport of Shiga toxin and ricin
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AbstractThe plant toxin ricin and the bacterial toxin Shiga toxin are not only a threat to human health but may also be used in cancer treatment and to gain new insight into the mechanisms of intracellular transport. Ricin and Shiga toxin are enzymes that exploit the endocytic pathway to kill the cells. They follow the retrograde transport route from early endosomes via the Golgi apparatus to the endoplasmic reticulum, and they are then translocated to the cytosol, where they inactivate ribosomes. This study has focused on new proteins important for transport of ricin and Shiga toxin from endosomes to the Golgi apparatus, and the sorting nexins SNX1, SNX2, and SNX4, as well as the Rab6 GTPase isoforms Rab6A and Rab6A’ have been identified as important factors in this transport. In addition, this work has revealed that Shiga toxin, by signaling through the Syk kinase, is able to increase the number of clathrin-coated pits on the cell surface.
List of Papers
I. Utskarpen, A, Slagsvold, HH, Iversen, TG, Wälchli, S, and Sandvig, K (2006) Transport of ricin from endosomes to the Golgi apparatus is regulated by Rab6A and Rab6A'. Traffic 7, 663-72.
II. Skånland, SS, Wälchli, S, Utskarpen, A, and Sandvig, K (2007) Phosphoinositide-regulated retrograde transport of ricin: Crosstalk between hVps34 and sorting nexins. Traffic 8, 297-309.
III. Utskarpen, A, Slagsvold, HH, Dyve, AB, Skånland, SS, and Sandvig, K (2007) SNX1 and SNX2 mediate retrograde transport of Shiga toxin. Biochem. Biophys. Res. Commun. 358, 566-70.
IV. Utskarpen, A, Massol, R, van Deurs, B, Lauvrak, SU, Kirchhausen, T, and Sandvig, K. Shiga toxin increases formation of clathrin coated pits through Syk kinase. Manuscript.