Ricin and Shiga toxin are protein toxins able to enter target cells by endocytosis. They can be transported via early endosomes to the Golgi apparatus and the endoplasmic reticulum. From this compartment, they are translocated to the cytosol where they inactivate ribosomes and thus kill the cell.
We have studied mechanisms involved in endosome to Golgi transport of ricin and Shiga toxin. We have found that Shiga toxin can induce signaling events which promote the toxin transport, and identified effectors of this pathway. When it comes to ricin, we have characterized several proteins important for its endosome to Golgi transport, and show how they act together to regulate endosome motility. These findings provide new knowledge on how molecules travel inside cells.
List of papers
I Skånland SS, Wälchli S, Utskarpen A, Wandinger-Ness A, Sandvig K (2007): Phosphoinositide-regulated retrograde transport of ricin: crosstalk between hVps34 and sorting nexins.
Traffic, 8, 297-309. (2007).
II Wälchli S, Skånland SS, Gregers TF, Lauvrak SU, Torgersen ML, Ying M, Kuroda S, Maturana A, Sandvig K (2008): The Mitogen-activated Protein Kinase p38 Links Shiga Toxin-dependent Signaling and Trafficking. Mol Biol Cell, 19, 95-104. (2008).
III Skånland SS, Wälchli S, Brech A, Sandvig K: SNX4 in complex with and dynein: implications for endosome movement. PLoS ONE, 4, e5935. (2009).
IV Skånland SS, Wälchli S, Sandvig K: beta-arrestins attenuate p38 mediated endosome to Golgi transport. Cell Microbiol, 11, 796-807. (2009).