eat-2;ire-1

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Genetic mutants with eat-2, ire-1 alterations

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Lifespan (days)
21.5
Lifespan change (compared to wild type)
15.59%
Phenotype
Inactivation of ire-1 shortened wild-type lifespan by an average of 22% and ire-1 knockdown shortened the extended lifespan caused by the eat-2 mutation by an average of less than 20%.
Lifespan comparisons
Double mutant eat-2(ad1116);ire-1(RNAi) has a lifespan of 21.5 days, while single mutant ire-1(RNAi) has a lifespan of 16.0 days, single mutant eat-2(ad1116) has a lifespan of 24.2 days and wild type has a lifespan of 18.6 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Lifespan (days)
19.8
Lifespan change (compared to wild type)
-1.49%
Phenotype
Inactivation of ire-1 shortened wild-type lifespan by an average of 22% and ire-1 knockdown shortened the extended lifespan caused by the eat-2 mutation by an average of less than 20%.
Lifespan comparisons
Double mutant eat-2(ad1116);ire-1(RNAi) has a lifespan of 19.8 days, while single mutant ire-1(RNAi) has a lifespan of 16.6 days, single mutant eat-2(ad1116) has a lifespan of 24.6 days and wild type has a lifespan of 20.1 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Lifespan (days)
18.4
Lifespan change (compared to wild type)
-14.02%
Phenotype
Inactivation of ire-1 shortened wild-type lifespan by an average of 22% and ire-1 knockdown shortened the extended lifespan caused by the eat-2 mutation by an average of less than 20%.
Lifespan comparisons
Double mutant eat-2(ad1116);ire-1(ok799) has a lifespan of 18.4 days, while single mutant ire-1(ok799) has a lifespan of 13.9 days, single mutant eat-2(ad1116) has a lifespan of 24.0 days and wild type has a lifespan of 21.4 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Lifespan (days)
19.7
Lifespan change (compared to wild type)
12.57%
Phenotype
Inactivation of ire-1 shortened wild-type lifespan by an average of 22% and ire-1 knockdown shortened the extended lifespan caused by the eat-2 mutation by an average of less than 20%.
Lifespan comparisons
Double mutant eat-2(ad1116);ire-1(ok799) has a lifespan of 19.7 days, while single mutant ire-1(ok799) has a lifespan of 10.9 days, single mutant eat-2(ad1116) has a lifespan of 24.3 days and wild type has a lifespan of 17.5 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Henis-Korenblit S et al., 2010, Insulin/IGF-1 signaling mutants reprogram ER stress response regulators to promote longevity. Proc Natl Acad Sci U S A. 107(21):9730-5 20460307 Click here to select all mutants from this PubMed ID in the graph
Abstract
When unfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response is activated. This ER stress response restores ER homeostasis by coordinating processes that decrease translation, degrade misfolded proteins, and increase the levels of ER-resident chaperones. Ribonuclease inositol-requiring protein-1 (IRE-1), an endoribonuclease that mediates unconventional splicing, and its target, the XBP-1 transcription factor, are key mediators of the unfolded protein response. In this study, we show that in Caenorhabditis elegans insulin/IGF-1 pathway mutants, IRE-1 and XBP-1 promote lifespan extension and enhance resistance to ER stress. We show that these effects are not achieved simply by increasing the level of spliced xbp-1 mRNA and expression of XBP-1's normal target genes. Instead, in insulin/IGF-1 pathway mutants, XBP-1 collaborates with DAF-16, a FOXO-transcription factor that is activated in these mutants, to enhance ER stress resistance and to activate new genes that promote longevity.

Search genes: eat-2 ire-1

Entrez ID
Symbol
GenAge
Wormbase ID

175072
eat-2
View on GenAge (eat-2)
WBGene00001133

Neuronal acetylcholine receptor subunit eat-2

Locus: CELE_Y48B6A.4

Wormbase description: eat-2 encodes a ligand-gated ion channel subunit most closely related to the non-alpha-subunits of nicotinic acetylcholine receptors (nAChR); EAT-2 functions postsynaptically in pharyngeal muscle to regulate the rate of pharyngeal pumping; eat-2 is also required for normal life span and defecation; a functional EAT-2::GFP fusion protein localizes to two small dots near the junction of pharyngeal muscles pm4 and pm5, which is the site of the posterior-most MC motor neuron processes and the MC synapse; eat-2 genetically interacts with eat-18, which encodes a predicted novel transmembrane protein expressed in pharyngeal muscle and required for proper function of pharyngeal nicotonic receptors.

Entrez ID
Symbol
GenAge
Wormbase ID

174305
ire-1
View on GenAge (ire-1)
WBGene00002147

IRE1 kinase related;Serine/threonine-protein kinase

Locus: CELE_C41C4.4

Wormbase description: ire-1 encodes a transmembrane serine/threonine protein kinase and site-specific endoribonuclease orthologous to Saccharomyces cerevisiae inositol-requiring 1 protein kinase (Ire1) and human endoplasmic reticulum-to-nucleus signaling 1 (ERN1, OMIM:604033); IRE-1 is required for the unfolded protein response (UPR) that counteracts cellular stress induced by accumulation of unfolded proteins in the endoplasmic reticulum (ER); in response to ER stress, IRE-1 cleaves xbp-1 mRNA to produce transcriptionally active XBP-1 that positively regulates UPR gene expression in order to maintain ER homeostasis.

Orthologs of eat-2;ire-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of eat-2 in SynergyAge

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Species	Gene

Orthologs of ire-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Ire1
Mus musculus	Ern1
Mus musculus	Ern2