glp-4;mpk-1

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Genetic mutants with glp-4, mpk-1 alterations

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

Temperature °C
25
Diet
NGM
Lifespan (days)
9.3
Lifespan change (compared to wild type)
-7.00%
Phenotype
RNAi inactivation of mpk-1 shortened the life span of germ line-defective glp-4(bn2ts) worms, indicating that the MPK-1 cascade functions to extend life span in C. elegans, independently of its role in germ line development.
Lifespan comparisons
Double mutant glp-4(bn2ts);mpk-1(RNAi) has a lifespan of 9.3 days, while single mutant mpk-1(RNAi) has a lifespan of 8.1 days, single mutant glp-4(bn2ts) has a lifespan of 11.97 days and wild type has a lifespan of 10.0 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Okuyama T et al., 2010, The ERK-MAPK pathway regulates longevity through SKN-1 and insulin-like signaling in Caenorhabditis elegans. J Biol Chem. 285(39):30274-81 20624915 Click here to select all mutants from this PubMed ID in the graph
Abstract
It has not been determined yet whether the ERK-MAPK pathway regulates longevity of metazoans. Here, we show that the Caenorhabditis elegans ERK cascade promotes longevity through the two longevity-promoting transcription factors, SKN-1 and DAF-16. We find that RNAi of three genes, which constitute the ERK cascade (lin-45/RAF1, mek-2/MEK1/2, and mpk-1/ERK1/2), results in reduction of life span. Moreover, RNAi of lip-1, the gene encoding a MAPK phosphatase that inactivates MPK-1, increases life span. Epistasis analyses show that the ERK (MPK-1) cascade-mediated life span extension requires SKN-1, whose function is mediated, at least partly, through DAF-2/DAF-16 insulin-like signaling. MPK-1 phosphorylates SKN-1 on the key sites that are required for SKN-1 nuclear accumulation. Our results also show that one mechanism by which SKN-1 regulates insulin-like signaling is through the regulation of expression of insulin-like peptides. Our findings thus identify a novel ERK-MAPK-mediated signaling pathway that promotes longevity.

Search genes: glp-4 mpk-1

Entrez ID
Symbol
GenAge
Wormbase ID

173224
glp-4
View on GenAge (glp-4)
WBGene00006936

Valine--tRNA ligase

Locus: CELE_Y87G2A.5

Wormbase description: vrs-2 encodes a predicted cytoplasmic valyl-tRNA synthetase (ValRS), a class I aminoacyl-tRNA synthetase that catalyzes the attachment of valine to its cognate tRNA and is thus required for protein biosynthesis; in C. elegans, VRS-2 activity is required for embryonic and germline development.

Entrez ID
Symbol
GenAge
Wormbase ID

175545
mpk-1
View on GenAge (mpk-1)
WBGene00003401

Mitogen-activated protein kinase mpk-1

Locus: CELE_F43C1.2

Wormbase description: mpk-1 encodes a mitogen-activated protein (MAP) kinase an ERK ortholog functioning in vulval cell fate specification, cell migration/guidance, defense against bacterial infection, and other processes; in proximal germline, sperm-dependent physiological MPK-1 activation results in phosphorylation based inactivation of NOS-3, FEM-CUL-2-mediated degradation of TRA-1 and the promotion of membrane organization during oogenesis; mpk-1 affect LET-60(Ras)-mediated induction of vulval cell fates, larval viability, morphology of the male spicules; both LIN-1 and LIN-31 act genetically downstream of mpk-1 with respect to vulval induction; MPK-1 is necessary for pachytene cell organization; mpk-1 mutants display germ cells arrested in pachytene; MPK-1 is necessary for the progression from distal to proximal pachytene; MPK-1 promotes pachytene progression, with the rise in dpMPK-1 triggering a transition from a distal pachytene to a proximal pachytene subtype; MPK-1 functions in the germline for meiotic prophase progression and gametogenesis; MPK-1 ERK signaling is necessary for the male germ cell fate; MPK-1 ERK has the nonessential function of promoting the proliferative germ cell fate; mpk-1 acts in combination with mek-2 to permit germ cell exit from the pachytene stage of first meiotic prophase; MPK-1 activation is temporally/spatially dynamic compared to relatively constant levels of total MPK-1.

Orthologs of glp-4;mpk-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	rl;ValRS
Mus musculus	Mapk1;Vars
Mus musculus	Mapk3;Vars
Mus musculus	Vars;Mapk1
Mus musculus	Vars;Mapk3

Orthologs of glp-4 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	ValRS
Mus musculus	Vars

Orthologs of mpk-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	rl
Mus musculus	Mapk1
Mus musculus	Mapk3