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

BiP Negatively Affects Ricin Transport

1,2,†
, 1,2,†
, 2,3
, 1
 and 1,2,4,*
Received: 22 March 2013; in revised form: 2 May 2013 / Accepted: 2 May 2013 / Published: 10 May 2013
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Abstract: 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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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

AMA Style

Gregers TF, Skånland SS, Wälchli S, Bakke O, Sandvig K. BiP Negatively Affects Ricin Transport. Toxins. 2013; 5(5):969-982.

Chicago/Turabian Style

Gregers, Tone F.; Skånland, Sigrid S.; Wälchli, Sébastien; Bakke, Oddmund; Sandvig, Kirsten. 2013. "BiP Negatively Affects Ricin Transport." Toxins 5, no. 5: 969-982.



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