eat-2;mxl-2

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Genetic mutants with eat-2, mxl-2 alterations

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

Temperature °C
20
Diet
HT115
Lifespan (days)
17.39
Lifespan change (compared to wild type)
-13.05%
Phenotype
RNAi inactivation of mxl-2 partially suppresses the extended lifespan observed in eat-2(ad465) mutants.
Lifespan comparisons
Double mutant eat-2(ad465);mxl-2(RNAi) has a lifespan of 17.39 days, while single mutant mxl-2(RNAi) has a lifespan of 19.13 days, single mutant eat-2(ad465) has a lifespan of 30.0 days and wild type has a lifespan of 20.0 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Johnson DW et al., 2014, The Caenorhabditis elegans Myc-Mondo/Mad complexes integrate diverse longevity signals. PLoS Genet. 10(4):e1004278 24699255 Click here to select all mutants from this PubMed ID in the graph
Abstract
The Myc family of transcription factors regulates a variety of biological processes, including the cell cycle, growth, proliferation, metabolism, and apoptosis. In Caenorhabditis elegans, the "Myc interaction network" consists of two opposing heterodimeric complexes with antagonistic functions in transcriptional control: the Myc-Mondo:Mlx transcriptional activation complex and the Mad:Max transcriptional repression complex. In C. elegans, Mondo, Mlx, Mad, and Max are encoded by mml-1, mxl-2, mdl-1, and mxl-1, respectively. Here we show a similar antagonistic role for the C. elegans Myc-Mondo and Mad complexes in longevity control. Loss of mml-1 or mxl-2 shortens C. elegans lifespan. In contrast, loss of mdl-1 or mxl-1 increases longevity, dependent upon MML-1:MXL-2. The MML-1:MXL-2 and MDL-1:MXL-1 complexes function in both the insulin signaling and dietary restriction pathways. Furthermore, decreased insulin-like/IGF-1 signaling (ILS) or conditions of dietary restriction increase the accumulation of MML-1, consistent with the notion that the Myc family members function as sensors of metabolic status. Additionally, we find that Myc family members are regulated by distinct mechanisms, which would allow for integrated control of gene expression from diverse signals of metabolic status. We compared putative target genes based on ChIP-sequencing data in the modENCODE project and found significant overlap in genomic DNA binding between the major effectors of ILS (DAF-16/FoxO), DR (PHA-4/FoxA), and Myc family (MDL-1/Mad/Mxd) at common target genes, which suggests that diverse signals of metabolic status converge on overlapping transcriptional programs that influence aging. Consistent with this, there is over-enrichment at these common targets for genes that function in lifespan, stress response, and carbohydrate metabolism. Additionally, we find that Myc family members are also involved in stress response and the maintenance of protein homeostasis. Collectively, these findings indicate that Myc family members integrate diverse signals of metabolic status, to coordinate overlapping metabolic and cytoprotective transcriptional programs that determine the progression of aging.

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

Temperature °C
20
Diet
HT115
Lifespan (days)
18.8
Lifespan change (compared to wild type)
-6.00%
Phenotype
The mxl-2(tm1516) null mutation partially suppresses the extended lifespan observed in eat-2(ad465) mutant animals.
Lifespan comparisons
Double mutant eat-2(ad465);mxl-2(tm1516) has a lifespan of 18.8 days, while single mutant mxl-2(tm1516) has a lifespan of 12.8 days, single mutant eat-2(ad465) has a lifespan of 30.0 days and wild type has a lifespan of 20.0 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Johnson DW et al., 2014, The Caenorhabditis elegans Myc-Mondo/Mad complexes integrate diverse longevity signals. PLoS Genet. 10(4):e1004278 24699255 Click here to select all mutants from this PubMed ID in the graph
Abstract
The Myc family of transcription factors regulates a variety of biological processes, including the cell cycle, growth, proliferation, metabolism, and apoptosis. In Caenorhabditis elegans, the "Myc interaction network" consists of two opposing heterodimeric complexes with antagonistic functions in transcriptional control: the Myc-Mondo:Mlx transcriptional activation complex and the Mad:Max transcriptional repression complex. In C. elegans, Mondo, Mlx, Mad, and Max are encoded by mml-1, mxl-2, mdl-1, and mxl-1, respectively. Here we show a similar antagonistic role for the C. elegans Myc-Mondo and Mad complexes in longevity control. Loss of mml-1 or mxl-2 shortens C. elegans lifespan. In contrast, loss of mdl-1 or mxl-1 increases longevity, dependent upon MML-1:MXL-2. The MML-1:MXL-2 and MDL-1:MXL-1 complexes function in both the insulin signaling and dietary restriction pathways. Furthermore, decreased insulin-like/IGF-1 signaling (ILS) or conditions of dietary restriction increase the accumulation of MML-1, consistent with the notion that the Myc family members function as sensors of metabolic status. Additionally, we find that Myc family members are regulated by distinct mechanisms, which would allow for integrated control of gene expression from diverse signals of metabolic status. We compared putative target genes based on ChIP-sequencing data in the modENCODE project and found significant overlap in genomic DNA binding between the major effectors of ILS (DAF-16/FoxO), DR (PHA-4/FoxA), and Myc family (MDL-1/Mad/Mxd) at common target genes, which suggests that diverse signals of metabolic status converge on overlapping transcriptional programs that influence aging. Consistent with this, there is over-enrichment at these common targets for genes that function in lifespan, stress response, and carbohydrate metabolism. Additionally, we find that Myc family members are also involved in stress response and the maintenance of protein homeostasis. Collectively, these findings indicate that Myc family members integrate diverse signals of metabolic status, to coordinate overlapping metabolic and cytoprotective transcriptional programs that determine the progression of aging.

Search genes: eat-2 mxl-2

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

175184
mxl-2
View on GenAge (mxl-2)
WBGene00003510

MaX-Like

Locus: CELE_F40G9.11

Wormbase description: none available

Orthologs of eat-2;mxl-2 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 mxl-2 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	bigmax
Mus musculus	Mlx