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Toxins 2013, 5(5), 969-982; doi:10.3390/toxins5050969

BiP Negatively Affects Ricin Transport

1 Department of Biosciences, and Centre for Immune Regulation, University of Oslo, Oslo 0316, Norway 2 Section of Biochemistry, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo 0379, Norway 3 Section of Immunology, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo 0379, Norway 4 Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo 0379, Norway These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 22 March 2013 / Revised: 2 May 2013 / Accepted: 2 May 2013 / Published: 10 May 2013
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The AB plant toxin ricin binds both glycoproteins and glycolipids at the cell surface via its B subunit. After binding, ricin is endocytosed and then transported retrogradely through the Golgi to the endoplasmic reticulum (ER). In the ER, the A subunit is retrotranslocated to the cytosol in a chaperone-dependent process, which is not fully explored. Recently two separate siRNA screens have demonstrated that ER chaperones have implications for ricin toxicity. ER associated degradation (ERAD) involves translocation of misfolded proteins from ER to cytosol and it is conceivable that protein toxins exploit this pathway. The ER chaperone BiP is an important ER regulator and has been implicated in toxicity mediated by cholera and Shiga toxin. In this study, we have investigated the role of BiP in ricin translocation to the cytosol. We first show that overexpression of BiP inhibited ricin translocation and protected cells against the toxin. Furthermore, shRNA-mediated depletion of BiP enhanced toxin translocation resulting in increased cytotoxicity. BiP-dependent inhibition of ricin toxicity was independent of ER stress. Our findings suggest that in contrast to what was shown with the Shiga toxin, the presence of BiP does not facilitate, but rather inhibits the entry of ricin into the cytosol.
Keywords: BiP; ricin; toxin; ER chaperones; endoplasmic reticulum; toxicity BiP; ricin; toxin; ER chaperones; endoplasmic reticulum; toxicity
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Gregers, T.F.; Skånland, S.S.; Wälchli, S.; Bakke, O.; Sandvig, K. BiP Negatively Affects Ricin Transport. Toxins 2013, 5, 969-982.

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