Physiological IRE-1-XBP-1 and PEK-1 Signaling in Caenorhabditis elegans Larval Development and Immunity
Endoplasmic reticulum (ER) stress activates the Unfolded Protein Response, a compensatory signaling response that is mediated by the IRE-1, PERK/PEK-1, and ATF-6 pathways in metazoans. Genetic studies have implicated roles for UPR signaling in animal development and disease, but the function of the...
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2012
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| Online Access: | http://hdl.handle.net/1721.1/69167 https://orcid.org/0000-0002-4109-5152 |
| _version_ | 1826216014093746176 |
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| author | Kim, Dennis H. Richardson, Claire Elissa Kinkel, Stephanie |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Kim, Dennis H. Richardson, Claire Elissa Kinkel, Stephanie |
| author_sort | Kim, Dennis H. |
| collection | MIT |
| description | Endoplasmic reticulum (ER) stress activates the Unfolded Protein Response, a compensatory signaling response that is mediated by the IRE-1, PERK/PEK-1, and ATF-6 pathways in metazoans. Genetic studies have implicated roles for UPR signaling in animal development and disease, but the function of the UPR under physiological conditions, in the absence of chemical agents administered to induce ER stress, is not well understood. Here, we show that in Caenorhabditis elegans XBP-1 deficiency results in constitutive ER stress, reflected by increased basal levels of IRE-1 and PEK-1 activity under physiological conditions. We define a dynamic, temperature-dependent requirement for XBP-1 and PEK-1 activities that increases with immune activation and at elevated physiological temperatures in C. elegans. Our data suggest that the negative feedback loops involving the activation of IRE-1-XBP-1 and PEK-1 pathways serve essential roles, not only at the extremes of ER stress, but also in the maintenance of ER homeostasis under physiological conditions. |
| first_indexed | 2024-09-23T16:40:56Z |
| format | Article |
| id | mit-1721.1/69167 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:40:56Z |
| publishDate | 2012 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/691672022-10-03T07:33:51Z Physiological IRE-1-XBP-1 and PEK-1 Signaling in Caenorhabditis elegans Larval Development and Immunity Kim, Dennis H. Richardson, Claire Elissa Kinkel, Stephanie Massachusetts Institute of Technology. Department of Biology Kim, Dennis H. Kim, Dennis H. Kinkel, Stephanie Ann Richardson, Claire Elissa Endoplasmic reticulum (ER) stress activates the Unfolded Protein Response, a compensatory signaling response that is mediated by the IRE-1, PERK/PEK-1, and ATF-6 pathways in metazoans. Genetic studies have implicated roles for UPR signaling in animal development and disease, but the function of the UPR under physiological conditions, in the absence of chemical agents administered to induce ER stress, is not well understood. Here, we show that in Caenorhabditis elegans XBP-1 deficiency results in constitutive ER stress, reflected by increased basal levels of IRE-1 and PEK-1 activity under physiological conditions. We define a dynamic, temperature-dependent requirement for XBP-1 and PEK-1 activities that increases with immune activation and at elevated physiological temperatures in C. elegans. Our data suggest that the negative feedback loops involving the activation of IRE-1-XBP-1 and PEK-1 pathways serve essential roles, not only at the extremes of ER stress, but also in the maintenance of ER homeostasis under physiological conditions. National Institutes of Health (U.S.) (grant R01-GM084477) 2012-02-23T17:49:12Z 2012-02-23T17:49:12Z 2011-11 2011-07 Article http://purl.org/eprint/type/JournalArticle 1553-7390 1553-7404 http://hdl.handle.net/1721.1/69167 Richardson, Claire E., Stephanie Kinkel, and Dennis H. Kim. “Physiological IRE-1-XBP-1 and PEK-1 Signaling in Caenorhabditis Elegans Larval Development and Immunity.” Ed. Kaveh Ashrafi. PLoS Genetics 7.11 (2011): e1002391. Web. 23 Feb. 2012. https://orcid.org/0000-0002-4109-5152 en_US http://dx.doi.org/10.1371/journal.pgen.1002391 PLoS Genetics Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Kim, Dennis H. Richardson, Claire Elissa Kinkel, Stephanie Physiological IRE-1-XBP-1 and PEK-1 Signaling in Caenorhabditis elegans Larval Development and Immunity |
| title | Physiological IRE-1-XBP-1 and PEK-1 Signaling in Caenorhabditis elegans Larval Development and Immunity |
| title_full | Physiological IRE-1-XBP-1 and PEK-1 Signaling in Caenorhabditis elegans Larval Development and Immunity |
| title_fullStr | Physiological IRE-1-XBP-1 and PEK-1 Signaling in Caenorhabditis elegans Larval Development and Immunity |
| title_full_unstemmed | Physiological IRE-1-XBP-1 and PEK-1 Signaling in Caenorhabditis elegans Larval Development and Immunity |
| title_short | Physiological IRE-1-XBP-1 and PEK-1 Signaling in Caenorhabditis elegans Larval Development and Immunity |
| title_sort | physiological ire 1 xbp 1 and pek 1 signaling in caenorhabditis elegans larval development and immunity |
| url | http://hdl.handle.net/1721.1/69167 https://orcid.org/0000-0002-4109-5152 |
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