eak-7;glp-1

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Genetic mutants with eak-7, glp-1 alterations

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

Diet
OP50
Lifespan (days)
49.7
Lifespan change (compared to wild type)
214.56%
Phenotype
Eak-7 null mutation enhances lifespan extension of glp-1(e2141) mutants.
Lifespan comparisons
Double mutant eak-7(tm3188);glp-1(e2141) has a lifespan of 49.7 days, while single mutant glp-1(e2141) has a lifespan of 27.6 days, single mutant eak-7(tm3188) has a lifespan of 20.8 days and wild type has a lifespan of 15.8 days.
Type of interaction
See methods
Synergistic (positive)
Citation
View abstract
Alam H et al., 2010, EAK-7 controls development and life span by regulating nuclear DAF-16/FoxO activity. Cell Metab. 12(1):30-41 20620993 Click here to select all mutants from this PubMed ID in the graph
Abstract
FoxO transcription factors control development and longevity in diverse species. Although FoxO regulation via changes in its subcellular localization is well established, little is known about how FoxO activity is regulated in the nucleus. Here, we show that the conserved C. elegans protein EAK-7 acts in parallel to the serine/threonine kinase AKT-1 to inhibit the FoxO transcription factor DAF-16. Loss of EAK-7 activity promotes diapause and longevity in a DAF-16/FoxO-dependent manner. Whereas akt-1 mutation activates DAF-16/FoxO by promoting its translocation from the cytoplasm to the nucleus, eak-7 mutation increases nuclear DAF-16/FoxO activity without influencing DAF-16/FoxO subcellular localization. Thus, EAK-7 and AKT-1 inhibit DAF-16/FoxO activity via distinct mechanisms. Our results implicate EAK-7 as a FoxO regulator and highlight the biological impact of a regulatory pathway that governs the activity of nuclear FoxO without altering its subcellular location.

Diet
OP50
Lifespan (days)
40.4
Lifespan change (compared to wild type)
120.77%
Phenotype
Eak-7 null mutation enhances lifespan extension of glp-1(e2141) mutants.
Lifespan comparisons
Double mutant eak-7(tm3188);glp-1(e2141) has a lifespan of 40.4 days, while single mutant glp-1(e2141) has a lifespan of 27.6 days, single mutant eak-7(tm3188) has a lifespan of 23.1 days and wild type has a lifespan of 18.3 days.
Type of interaction
See methods
Synergistic (positive)
Citation
View abstract
Alam H et al., 2010, EAK-7 controls development and life span by regulating nuclear DAF-16/FoxO activity. Cell Metab. 12(1):30-41 20620993 Click here to select all mutants from this PubMed ID in the graph
Abstract
FoxO transcription factors control development and longevity in diverse species. Although FoxO regulation via changes in its subcellular localization is well established, little is known about how FoxO activity is regulated in the nucleus. Here, we show that the conserved C. elegans protein EAK-7 acts in parallel to the serine/threonine kinase AKT-1 to inhibit the FoxO transcription factor DAF-16. Loss of EAK-7 activity promotes diapause and longevity in a DAF-16/FoxO-dependent manner. Whereas akt-1 mutation activates DAF-16/FoxO by promoting its translocation from the cytoplasm to the nucleus, eak-7 mutation increases nuclear DAF-16/FoxO activity without influencing DAF-16/FoxO subcellular localization. Thus, EAK-7 and AKT-1 inhibit DAF-16/FoxO activity via distinct mechanisms. Our results implicate EAK-7 as a FoxO regulator and highlight the biological impact of a regulatory pathway that governs the activity of nuclear FoxO without altering its subcellular location.

Search genes: eak-7 glp-1

Entrez ID
Symbol
GenAge
Wormbase ID

3564920
eak-7
View on GenAge (eak-7)
WBGene00010671

Enhancer of AKt-1 null

Locus: CELE_K08E7.1

Wormbase description: eak-7 encodes a conserved protein that contains a TLDc (TBC and LysM domain-containing) domain and an N-myristoylation motif; EAK-7 negatively regulates dauer formation and longevity by controlling the nuclear activity of the DAF-16/FoxO transcription factor; an EAK-7::GFP is widely expressed and localizes to the plasma membrane.

Entrez ID
Symbol
GenAge
Wormbase ID

176286
glp-1
View on GenAge (glp-1)
WBGene00001609

Protein glp-1

Locus: CELE_F02A9.6

Wormbase description: glp-1 encodes an N-glycosylated transmembrane protein that, along with LIN-12, comprises one of two C. elegans members of the LIN-12/Notch family of receptors; from the N- to the C-terminus, GLP-1 is characterized by ten extracellular EGF-like repeats, three LIN-12/Notch repeats, a CC-linker, a transmembrane domain, a RAM domain, six intracellular ankyrin repeats, and a PEST sequence; in C. elegans, GLP-1 activity is required for cell fate specification in germline and somatic tissues; in the germline, GLP-1, acting as a receptor for the DSL family ligand LAG-2, is essential for mitotic proliferation of germ cells and maintenance of germline stem cells; in somatic tissues, maternally provided GLP-1, acting as a receptor for the DSL family ligand APX-1, is required for inductive interactions that specify the fates of certain embryonic blastomeres; GLP-1 is also required for some later embryonic cell fate decisions, and in these decisions its activity is functionally redundant with that of LIN-12; GLP-1 expression is regulated temporally and spatially via translational control, as GLP-1 mRNA, present ubiquitously in the germline and embryo, yields detectable protein solely in lateral, interior, and endomembranes of distal, mitotic germ cells, and then predominantly in the AB blastomere and its descendants in the early embryo; proper spatial translation of glp-1 mRNA in the embryo is dependent upon genes such as the par genes, that are required for normal anterior-posterior asymmetry in the early embryo; signaling through GLP-1 controls the activity of the downstream Notch pathway components LAG-3 and LAG-1, the latter being predicted to function as part of a transcriptional feedback mechanism that positively regulates GLP-1 expression; signaling through the DNA-binding protein LAG-1 is believed to involve a direct interaction between LAG-1 and the GLP-1 RAM and ankyrin domains

Orthologs of eak-7;glp-1 in SynergyAge

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Species	Gene

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Species	Gene

Orthologs of eak-7 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	CG5149

Orthologs of glp-1 in SynergyAge

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Species	Gene