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The ERdj5-Sel1L complex facilitates cholera toxin retrotranslocation

Cholera toxin (CT) traffics from the host cell surface to the endoplasmic reticulum (ER), where the toxin's catalytic CTA1 subunit retrotranslocates to the cytosol to induce toxicity. In the ER, CT is captured by the E3 ubiquitin ligase Hrd1 via an undefined mechanism to prepare for retrotransl...

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Detalles Bibliográficos
Autores principales: Williams, Jeffrey M., Inoue, Takamasa, Banks, Lindsey, Tsai, Billy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596249/
https://www.ncbi.nlm.nih.gov/pubmed/23363602
http://dx.doi.org/10.1091/mbc.E12-07-0522
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author Williams, Jeffrey M.
Inoue, Takamasa
Banks, Lindsey
Tsai, Billy
author_facet Williams, Jeffrey M.
Inoue, Takamasa
Banks, Lindsey
Tsai, Billy
author_sort Williams, Jeffrey M.
collection PubMed
description Cholera toxin (CT) traffics from the host cell surface to the endoplasmic reticulum (ER), where the toxin's catalytic CTA1 subunit retrotranslocates to the cytosol to induce toxicity. In the ER, CT is captured by the E3 ubiquitin ligase Hrd1 via an undefined mechanism to prepare for retrotranslocation. Using loss-of-function and gain-of-function approaches, we demonstrate that the ER-resident factor ERdj5 promotes CTA1 retrotranslocation, in part, via its J domain. This Hsp70 cochaperone regulates binding between CTA and the ER Hsp70 BiP, a chaperone previously implicated in toxin retrotranslocation. Importantly, ERdj5 interacts with the Hrd1 adaptor Sel1L directly through Sel1L's N-terminal lumenal domain, thereby linking ERdj5 to the Hrd1 complex. Sel1L itself also binds CTA and facilitates toxin retrotranslocation. By contrast, EDEM1 and OS-9, two established Sel1L binding partners, do not play significant roles in CTA1 retrotranslocation. Our results thus identify two ER factors that promote ER-to-cytosol transport of CTA1. They also indicate that ERdj5, by binding to Sel1L, triggers BiP–toxin interaction proximal to the Hrd1 complex. We postulate this scenario enables the Hrd1-associated retrotranslocation machinery to capture the toxin efficiently once the toxin is released from BiP.
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spelling pubmed-35962492013-05-30 The ERdj5-Sel1L complex facilitates cholera toxin retrotranslocation Williams, Jeffrey M. Inoue, Takamasa Banks, Lindsey Tsai, Billy Mol Biol Cell Articles Cholera toxin (CT) traffics from the host cell surface to the endoplasmic reticulum (ER), where the toxin's catalytic CTA1 subunit retrotranslocates to the cytosol to induce toxicity. In the ER, CT is captured by the E3 ubiquitin ligase Hrd1 via an undefined mechanism to prepare for retrotranslocation. Using loss-of-function and gain-of-function approaches, we demonstrate that the ER-resident factor ERdj5 promotes CTA1 retrotranslocation, in part, via its J domain. This Hsp70 cochaperone regulates binding between CTA and the ER Hsp70 BiP, a chaperone previously implicated in toxin retrotranslocation. Importantly, ERdj5 interacts with the Hrd1 adaptor Sel1L directly through Sel1L's N-terminal lumenal domain, thereby linking ERdj5 to the Hrd1 complex. Sel1L itself also binds CTA and facilitates toxin retrotranslocation. By contrast, EDEM1 and OS-9, two established Sel1L binding partners, do not play significant roles in CTA1 retrotranslocation. Our results thus identify two ER factors that promote ER-to-cytosol transport of CTA1. They also indicate that ERdj5, by binding to Sel1L, triggers BiP–toxin interaction proximal to the Hrd1 complex. We postulate this scenario enables the Hrd1-associated retrotranslocation machinery to capture the toxin efficiently once the toxin is released from BiP. The American Society for Cell Biology 2013-03-15 /pmc/articles/PMC3596249/ /pubmed/23363602 http://dx.doi.org/10.1091/mbc.E12-07-0522 Text en © 2013 Williams et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Williams, Jeffrey M.
Inoue, Takamasa
Banks, Lindsey
Tsai, Billy
The ERdj5-Sel1L complex facilitates cholera toxin retrotranslocation
title The ERdj5-Sel1L complex facilitates cholera toxin retrotranslocation
title_full The ERdj5-Sel1L complex facilitates cholera toxin retrotranslocation
title_fullStr The ERdj5-Sel1L complex facilitates cholera toxin retrotranslocation
title_full_unstemmed The ERdj5-Sel1L complex facilitates cholera toxin retrotranslocation
title_short The ERdj5-Sel1L complex facilitates cholera toxin retrotranslocation
title_sort erdj5-sel1l complex facilitates cholera toxin retrotranslocation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596249/
https://www.ncbi.nlm.nih.gov/pubmed/23363602
http://dx.doi.org/10.1091/mbc.E12-07-0522
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