akt-1;eak-3

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Genetic mutants with akt-1, eak-3 alterations

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

Temperature °C
25
Lifespan (days)
12.64
Lifespan change (compared to wild type)
0.64%
Phenotype
Neither eak-3(mg344) nor eak-3;akt-1 double mutants lived longer than wild-type animals. eak-3;akt-1 animals had slightly shorter lifespans than akt-1(mg306) single mutants.
Lifespan comparisons
Double mutant akt-1(mg306);eak-3(mg344) has a lifespan of 12.64 days, while single mutant akt-1(mg306) has a lifespan of 13.49 days, single mutant eak-3(mg344) has a lifespan of 11.84 days and wild type has a lifespan of 12.56 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
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.

Temperature °C
20
Lifespan (days)
13.0
Lifespan change (compared to wild type)
2.36%
Phenotype
eak-3;akt-1 animals had slightly shorter lifespans than akt-1(mg306) single mutants. Neither eak-3(mg344) nor eak-3;akt-1 double mutants lived longer than wild-type animals. eak;akt-1 double mutants had lifespans comparable to eak-3 single.
Lifespan comparisons
Double mutant akt-1(mg306);eak-3(mg344) has a lifespan of 13.0 days, while single mutant akt-1(mg306) has a lifespan of 13.7 days, single mutant eak-3(mg344) has a lifespan of 13.7 days and wild type has a lifespan of 12.7 days.
Type of interaction
See methods
Antagonistic (positive)
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: akt-1 eak-3

Entrez ID
Symbol
GenAge
Wormbase ID

179424
akt-1
View on GenAge (akt-1)
WBGene00000102

Serine/threonine-protein kinase akt-1

Locus: CELE_C12D8.10

Wormbase description: akt-1 encodes an ortholog of the serine/threonine kinase Akt/PKB; akt-1 genetically interacts with the insulin signaling pathway and functions to regulate such processes as dauer larval development and salt chemotaxis learning; AKT-1 binds calmodulin in vitro in a calcium-dependent manner; an AKT-1::GFP fusion protein is widely expressed beginning in late stage embryos and continuing through adulthood; expression is seen in head, tail, and dorsal and ventral cord neurons, with additional expression seen in other cells including those of the pharynx, hypodermis, intestine, and spermatheca; two alleles of akt-1 (sa573 and sa700) have a Daf-c mutant phenotype at 27 degrees C (Hid phenotype).

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 akt-1;eak-3 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of akt-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Akt1
Mus musculus	Akt1
Mus musculus	Akt2
Mus musculus	Akt3

Orthologs of eak-3 in SynergyAge

Show in SynergyAge
Species	Gene