cup-4;skn-1

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Genetic mutants with cup-4, skn-1 alterations

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

Temperature °C
20
Diet
NGM
Lifespan (days)
17.6
Lifespan change (compared to wild type)
-20.00%
Lifespan comparisons
Double mutant cup-4(ok837);skn-1(RNAi) has a lifespan of 17.6 days, while single mutant cup-4(ok837) has a lifespan of 18.0 days and wild type has a lifespan of 22.0 days.
Type of interaction
See methods
Partially known monotony. Negative epistasis
Citation
View abstract
Park SK et al., 2010, Life-span extension by dietary restriction is mediated by NLP-7 signaling and coelomocyte endocytosis in C. elegans. FASEB J. 24(2):383-92 19783783 Click here to select all mutants from this PubMed ID in the graph
Abstract
Recent studies have shown that the rate of aging can be modulated by diverse interventions. Dietary restriction is the most widely used intervention to promote longevity; however, the mechanisms underlying the effect of dietary restriction remain elusive. In a previous study, we identified two novel genes, nlp-7 and cup-4, required for normal longevity in Caenorhabditis elegans. nlp-7 is one of a set of neuropeptide-like protein genes; cup-4 encodes an ion-channel involved in endocytosis by coelomocytes. Here, we assess whether nlp-7 and cup-4 mediate longevity increases by dietary restriction. RNAi of nlp-7 or cup-4 significantly reduces the life span of the eat-2 mutant, a genetic model of dietary restriction, but has no effect on the life span of long-lived mutants resulting from reduced insulin/IGF-1 signaling or dysfunction of the mitochondrial electron transport chain. The life-span extension observed in wild-type N2 worms by dietary restriction using bacterial dilution is prevented significantly in nlp-7 and cup-4 mutants. RNAi knockdown of genes encoding candidate receptors of NLP-7 and genes involved in endocytosis by coelomocytes also specifically shorten the life span of the eat-2 mutant. We conclude that two novel pathways, NLP-7 signaling and endocytosis by coelomocytes, are required for life extension under dietary restriction in C. elegans.

Temperature °C
20
Diet
NGM
Lifespan (days)
15.1
Lifespan change (compared to wild type)
-31.67%
Lifespan comparisons
Double mutant cup-4(ok837);skn-1(RNAi) has a lifespan of 15.1 days, while single mutant cup-4(ok837) has a lifespan of 17.0 days and wild type has a lifespan of 22.1 days.
Type of interaction
See methods
Partially known monotony. Negative epistasis
Citation
View abstract
Park SK et al., 2010, Life-span extension by dietary restriction is mediated by NLP-7 signaling and coelomocyte endocytosis in C. elegans. FASEB J. 24(2):383-92 19783783 Click here to select all mutants from this PubMed ID in the graph
Abstract
Recent studies have shown that the rate of aging can be modulated by diverse interventions. Dietary restriction is the most widely used intervention to promote longevity; however, the mechanisms underlying the effect of dietary restriction remain elusive. In a previous study, we identified two novel genes, nlp-7 and cup-4, required for normal longevity in Caenorhabditis elegans. nlp-7 is one of a set of neuropeptide-like protein genes; cup-4 encodes an ion-channel involved in endocytosis by coelomocytes. Here, we assess whether nlp-7 and cup-4 mediate longevity increases by dietary restriction. RNAi of nlp-7 or cup-4 significantly reduces the life span of the eat-2 mutant, a genetic model of dietary restriction, but has no effect on the life span of long-lived mutants resulting from reduced insulin/IGF-1 signaling or dysfunction of the mitochondrial electron transport chain. The life-span extension observed in wild-type N2 worms by dietary restriction using bacterial dilution is prevented significantly in nlp-7 and cup-4 mutants. RNAi knockdown of genes encoding candidate receptors of NLP-7 and genes involved in endocytosis by coelomocytes also specifically shorten the life span of the eat-2 mutant. We conclude that two novel pathways, NLP-7 signaling and endocytosis by coelomocytes, are required for life extension under dietary restriction in C. elegans.

Search genes: cup-4 skn-1

Entrez ID
Symbol
GenAge
Wormbase ID

176104
cup-4
View on GenAge (cup-4)
WBGene00000845

Acetylcholine receptor-like protein cup-4

Locus: CELE_C02C2.3

Wormbase description: cup-4 encodes a non-alpha ligand-gated ion channel with similarity to the nicotinic acetylcholine receptors; cup-4 is required cell autonomously for efficient fluid endocytosis in coelomocytes; cup-4 mutant animals display reduced levels of plasma membrane phosphatidylinositol 4,5-bisphosphate, suggesting that CUP-4 may regulate endocytosis via regulation of phospholipase C activity; in addition, cup-4 mutants display disorganized clathrin and RME-1 at the coelomocyte plasma membrane; CUP-4::GFP is expressed in coelomocytes where it localizes to the cytoplasm, primarily to cytoplasmic vesicles.

Entrez ID
Symbol
GenAge
Wormbase ID

177343
skn-1
View on GenAge (skn-1)
WBGene00004804

Protein skinhead-1;SKiNhead

Locus: CELE_T19E7.2

Wormbase description: skn-1 encodes a bZip transcription factor orthologous to the mammalian Nrf (Nuclear factor-erythroid-related factor) transcription factors; during early embryogenesis, maternally provided SKN-1 is required for specification of the EMS blastomere, a mesendodermal precursor that gives rise to pharyngeal, muscle, and intestinal cells; later, during postembryonic development, SKN-1 functions in the p38 MAPK pathway to regulate the oxidative stress response and in parallel to DAF-16/FOXO in the DAF-2-mediated insulin/IGF-1-like signaling pathway to regulate adult lifespan; in vitro assays indicate that SKN-1 can be directly phosphorylated by the AKT-1, AKT-2, and SGK-1 kinases that lie downstream of DAF-2 in the insulin signaling pathway and in vivo experiments suggest that this phosphorylation is essential for regulation of SKN-1 nuclear accumulation and hence, transcriptional regulator activity; in the early embryo, SKN-1 is detected at highest levels in nuclei of the P1 blastomere and its descendants through the 8-cell stage of embryogenesis; later in embryogenesis, SKN-1 is observed in all hypodermal and intestinal nuclei, with reporter constructs indicating that intestinal expression begins as early as the 50-100-cell stage; in larvae and young adults, SKN-1::GFP reporters are expressed in the intestine and ASI neurons, with expression in intestinal nuclei enhanced under conditions of stress or reduced DAF-2 signaling.

Orthologs of cup-4;skn-1 in SynergyAge

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Species	Gene

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Species	Gene

Orthologs of cup-4 in SynergyAge

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Species	Gene

Orthologs of skn-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Nfe2
Mus musculus	Nfe2l2
Mus musculus	Nfe2l1