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BiP Negatively Affects Ricin Transport

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 chaper...

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Autores principales: Gregers, Tone F., Skånland, Sigrid S., Wälchli, Sébastien, Bakke, Oddmund, Sandvig, Kirsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709273/
https://www.ncbi.nlm.nih.gov/pubmed/23666197
http://dx.doi.org/10.3390/toxins5050969
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author Gregers, Tone F.
Skånland, Sigrid S.
Wälchli, Sébastien
Bakke, Oddmund
Sandvig, Kirsten
author_facet Gregers, Tone F.
Skånland, Sigrid S.
Wälchli, Sébastien
Bakke, Oddmund
Sandvig, Kirsten
author_sort Gregers, Tone F.
collection PubMed
description 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.
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spelling pubmed-37092732013-07-12 BiP Negatively Affects Ricin Transport Gregers, Tone F. Skånland, Sigrid S. Wälchli, Sébastien Bakke, Oddmund Sandvig, Kirsten Toxins (Basel) Article 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. MDPI 2013-05-10 /pmc/articles/PMC3709273/ /pubmed/23666197 http://dx.doi.org/10.3390/toxins5050969 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Gregers, Tone F.
Skånland, Sigrid S.
Wälchli, Sébastien
Bakke, Oddmund
Sandvig, Kirsten
BiP Negatively Affects Ricin Transport
title BiP Negatively Affects Ricin Transport
title_full BiP Negatively Affects Ricin Transport
title_fullStr BiP Negatively Affects Ricin Transport
title_full_unstemmed BiP Negatively Affects Ricin Transport
title_short BiP Negatively Affects Ricin Transport
title_sort bip negatively affects ricin transport
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709273/
https://www.ncbi.nlm.nih.gov/pubmed/23666197
http://dx.doi.org/10.3390/toxins5050969
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