daf-16;eak-3

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Genetic mutants with daf-16, eak-3 alterations

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

Temperature °C
20
Lifespan (days)
16.24
Lifespan change (compared to wild type)
-36.24%
Phenotype
eak-3 mutation did not affect the lifespan of daf-16/FoxO mutants, suggesting that the lifespan extending effects of eak-3 mutation in a daf-2(e1370) background are mediated by DAF-16/FoxO.
Lifespan comparisons
Double mutant daf-16(mgDf47);eak-3(mg345) has a lifespan of 16.24 days, while single mutant daf-16(mgDf47) has a lifespan of 15.97 days, single mutant eak-3(mg345) has a lifespan of 24.54 days and wild type has a lifespan of 25.47 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Zhang Y et al., 2008, Caenorhabditis elegans EAK-3 inhibits dauer arrest via nonautonomous regulation of nuclear DAF-16/FoxO activity. Dev Biol. 315(2):290-302 18241854 Click here to select all mutants from this PubMed ID in the graph
Abstract
Insulin regulates development, metabolism, and lifespan via a conserved PI3K/Akt pathway that promotes cytoplasmic sequestration of FoxO transcription factors. The regulation of nuclear FoxO is poorly understood. In the nematode Caenorhabditis elegans, insulin-like signaling functions in larvae to inhibit dauer arrest and acts during adulthood to regulate lifespan. In a screen for genes that modulate C. elegans insulin-like signaling, we identified eak-3, which encodes a novel protein that is specifically expressed in the two endocrine XXX cells. The dauer arrest phenotype of eak-3 mutants is fully suppressed by mutations in daf-16/FoxO, which encodes the major target of C. elegans insulin-like signaling, and daf-12, which encodes a nuclear receptor regulated by steroid hormones known as dafachronic acids. eak-3 mutation does not affect DAF-16/FoxO subcellular localization but enhances expression of the direct DAF-16/FoxO target sod-3 in a daf-16/FoxO- and daf-12-dependent manner. eak-3 mutants have normal lifespans, suggesting that EAK-3 decouples insulin-like regulation of development and longevity. We propose that EAK-3 activity in the XXX cells promotes the synthesis and/or secretion of a hormone that acts in parallel to AKT-1 to inhibit the expression of DAF-16/FoxO target genes. Similar hormonal pathways may regulate FoxO target gene expression in mammals.

Search genes: daf-16 eak-3

Entrez ID
Symbol
GenAge
Wormbase ID

172981
daf-16
View on GenAge (daf-16)
WBGene00000912

Forkhead box protein O;hypothetical protein

Locus: CELE_R13H8.1

Wormbase description: daf-16 encodes the sole C. elegans forkhead box O (FOXO) homologue; DAF-16 functions as a transcription factor that acts in the insulin/IGF-1-mediated signaling (IIS) pathway that regulates dauer formation, longevity, fat metabolism, stress response, and innate immunity; DAF-16 regulates these various processes through isoform-specific expression, isoform-specific regulation by different AKT kinases, and differential regulation of target genes; DAF-16 can interact with the CBP-1 transcription cofactor in vitro, and interacts genetically with other genes in the insulin signaling and with daf-12, which encodes a nuclear hormone receptor; DAF-16 is activated in response to DNA damage during development and co-regulated by EGL-27, alleviates DNA-damage-induced developmental arrest by inducing DAF-16-associated element (DAE)-regulated genes; DAF-16 is broadly expressed but displays isoform-specific tissue enrichment; DAF-16 localizes to both the cytoplasm and the nucleus, with the ratio between the two an important regulator of function.

Entrez ID
Symbol
GenAge
Wormbase ID

190782
eak-3
View on GenAge (eak-3)
WBGene00022356

Enhancer of AKt-1 null

Locus: CELE_Y92C3A.3

Wormbase description: eak-3 encodes a protein required for the subset of DAF-16 functions controlling dauer development, but not for lifespan regulation; EAK-3 is expressed in XXX cells, and localizes to the plasma membrane, probably by N-terminal myristoylation; EAK-3 acts in a genetic pathway parallel to that of AKT-1, which may include AKT-2, EAK-4, EAK-6, or SDF-9; EAK-3 has no homologs outside of C. elegans itself, has 20% leucine-like residues, and has a single predicted coiled-coil domain; eak-3 mutants have a very weak dauer arrest phenotype at 25 deg. C., but strongly enhance the dauer arrest phenotype of akt-1(mg306), and enhances expression of the DAF-16 target sod-3; eak-3's dauer arrest and sod-3 overexpression phenotypes require DAF-12 and DAF-16; however, EAK-3 has no effect on lifespan.

Orthologs of daf-16;eak-3 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of daf-16 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6
Mus musculus	Foxo1
Mus musculus	Foxo4
Mus musculus	Foxo3

Orthologs of eak-3 in SynergyAge

Show in SynergyAge
Species	Gene