The Unfolded Protein Response in a Pair of Sensory Neurons Promotes Entry of C. elegans into Dauer Diapause
In response to unfavorable environmental conditions such as starvation, crowding, and elevated temperature, Caenorhabditis elegans larvae enter an alternative developmental stage known as dauer [ 1], which is characterized by adaptive changes in stress resistance and metabolism [ 2 ; 3]. The geneti...
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| Formáid: | Alt |
| Teanga: | en_US |
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Elsevier
2017
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| Rochtain ar líne: | http://hdl.handle.net/1721.1/110372 https://orcid.org/0000-0002-2994-8220 https://orcid.org/0000-0002-4109-5152 |
| _version_ | 1826205837808369664 |
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| author | Kulalert, Warakorn Kim, Dennis H. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Kulalert, Warakorn Kim, Dennis H. |
| author_sort | Kulalert, Warakorn |
| collection | MIT |
| description | In response to unfavorable environmental conditions such as starvation, crowding, and elevated temperature, Caenorhabditis elegans larvae enter an alternative developmental stage known as dauer [ 1], which is characterized by adaptive changes in stress resistance and metabolism [ 2 ; 3]. The genetic dissection of the molecular mechanisms of the C. elegans dauer developmental decision has defined evolutionarily conserved signaling pathways of organismal neuroendocrine physiology [ 2; 3 ; 4]. Here, we have identified a mechanism by which a dominant mutation in a neuronal insulin gene, daf-28(sa191) [ 5; 6 ; 7], causes constitutive entry into dauer diapause. We demonstrate that expression of the mutant DAF-28 insulin peptide results in endoplasmic reticulum (ER) stress in the ASI pair of chemosensory neurons. The neuronal ER stress does not compromise cellular survival but activates PEK-1, the C. elegans ortholog of the mammalian eIF2α kinase PERK, which in turn phosphorylates Ser49 of eIF2α, specifically in the ASI neuron pair, to promote entry into dauer diapause. Our data establish a novel role for ER stress and the unfolded protein response (UPR) in promoting entry into dauer diapause and suggest that, in addition to cell-autonomous activities in the maintenance of ER homeostasis, the UPR may act in a non-cell-autonomous manner to promote organismal adaptation to stress during larval development. |
| first_indexed | 2024-09-23T13:20:12Z |
| format | Article |
| id | mit-1721.1/110372 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:20:12Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1103722022-10-01T14:36:57Z The Unfolded Protein Response in a Pair of Sensory Neurons Promotes Entry of C. elegans into Dauer Diapause Kulalert, Warakorn Kim, Dennis H. Massachusetts Institute of Technology. Department of Biology Kulalert, Warakorn Kim, Dennis H. In response to unfavorable environmental conditions such as starvation, crowding, and elevated temperature, Caenorhabditis elegans larvae enter an alternative developmental stage known as dauer [ 1], which is characterized by adaptive changes in stress resistance and metabolism [ 2 ; 3]. The genetic dissection of the molecular mechanisms of the C. elegans dauer developmental decision has defined evolutionarily conserved signaling pathways of organismal neuroendocrine physiology [ 2; 3 ; 4]. Here, we have identified a mechanism by which a dominant mutation in a neuronal insulin gene, daf-28(sa191) [ 5; 6 ; 7], causes constitutive entry into dauer diapause. We demonstrate that expression of the mutant DAF-28 insulin peptide results in endoplasmic reticulum (ER) stress in the ASI pair of chemosensory neurons. The neuronal ER stress does not compromise cellular survival but activates PEK-1, the C. elegans ortholog of the mammalian eIF2α kinase PERK, which in turn phosphorylates Ser49 of eIF2α, specifically in the ASI neuron pair, to promote entry into dauer diapause. Our data establish a novel role for ER stress and the unfolded protein response (UPR) in promoting entry into dauer diapause and suggest that, in addition to cell-autonomous activities in the maintenance of ER homeostasis, the UPR may act in a non-cell-autonomous manner to promote organismal adaptation to stress during larval development. National Institutes of Health (U.S.) (grant GM084477) Lawrence Ellison Foundation (Ellison New Scholar in Aging Award) 2017-06-29T17:35:26Z 2017-06-29T17:35:26Z 2013-12 2013-10 Article http://purl.org/eprint/type/JournalArticle 0960-9822 1879-0445 http://hdl.handle.net/1721.1/110372 Kulalert, Warakorn, and Dennis H. Kim. “The Unfolded Protein Response in a Pair of Sensory Neurons Promotes Entry of C.?elegans into Dauer Diapause.” Current Biology 23.24 (2013): 2540–2545. https://orcid.org/0000-0002-2994-8220 https://orcid.org/0000-0002-4109-5152 en_US http://dx.doi.org/10.1016/j.cub.2013.10.058 Current Biology Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Kulalert, Warakorn Kim, Dennis H. The Unfolded Protein Response in a Pair of Sensory Neurons Promotes Entry of C. elegans into Dauer Diapause |
| title | The Unfolded Protein Response in a Pair of Sensory Neurons Promotes Entry of C. elegans into Dauer Diapause |
| title_full | The Unfolded Protein Response in a Pair of Sensory Neurons Promotes Entry of C. elegans into Dauer Diapause |
| title_fullStr | The Unfolded Protein Response in a Pair of Sensory Neurons Promotes Entry of C. elegans into Dauer Diapause |
| title_full_unstemmed | The Unfolded Protein Response in a Pair of Sensory Neurons Promotes Entry of C. elegans into Dauer Diapause |
| title_short | The Unfolded Protein Response in a Pair of Sensory Neurons Promotes Entry of C. elegans into Dauer Diapause |
| title_sort | unfolded protein response in a pair of sensory neurons promotes entry of c elegans into dauer diapause |
| url | http://hdl.handle.net/1721.1/110372 https://orcid.org/0000-0002-2994-8220 https://orcid.org/0000-0002-4109-5152 |
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