daf-16;unc-31

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Genetic mutants with daf-16, unc-31 alterations

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

Temperature °C
20
Lifespan (days)
19.0
Lifespan change (compared to wild type)
-13.64%
Phenotype
daf-16(m27) suppressed the life span extension of both unc-64(e246) and unc-31(e928)
Lifespan comparisons
Double mutant daf-16(m27);unc-31(e928) has a lifespan of 19 days, while single mutant unc-31(e928) has a lifespan of 29 days and wild type has a lifespan of 22 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Ailion M et al., 1999, Neurosecretory control of aging in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 96(13):7394-7 10377425 Click here to select all mutants from this PubMed ID in the graph
Abstract
In the nematode Caenorhabditis elegans, an insulin receptor signaling pathway regulates adult life span and developmental arrest at the dauer larval stage. Here we show that the unc-64 and unc-31 genes also function in this pathway. These two genes are involved in mediating Ca2+-regulated secretion. Mutations in unc-64 and unc-31 increase adult life span and cause constitutive dauer formation. Both phenotypes are suppressed by mutations in daf-16, which also suppresses other mutations in this pathway. We present evidence that the site of action of unc-64 is neuronal, suggesting that a neurosecretory signal regulates life span and dauer formation.

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

Temperature °C
23
Diet
Starvation
Lifespan (days)
7.6
Lifespan change (compared to wild type)
-39.20%
Phenotype
Loss of DAF-16/FOXO transcription factor, on L1 starvation survival.
Lifespan comparisons
Double mutant daf-16(mgDf47);unc-31(ft1) has a lifespan of 7.6 days, while single mutant unc-31(ft1) has a lifespan of 23.6 days, single mutant daf-16(mgDf47) has a lifespan of 7.5 days and wild type has a lifespan of 12.5 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Lee BH, Ashrafi K, 2008, A TRPV channel modulates C. elegans neurosecretion, larval starvation survival, and adult lifespan. PLoS Genet. 4(10):e1000213 18846209 Click here to select all mutants from this PubMed ID in the graph
Abstract
For most organisms, food is only intermittently available; therefore, molecular mechanisms that couple sensation of nutrient availability to growth and development are critical for survival. These mechanisms, however, remain poorly defined. In the absence of nutrients, newly hatched first larval (L1) stage Caenorhabditis elegans halt development and survive in this state for several weeks. We isolated mutations in unc-31, encoding a calcium-activated regulator of neural dense-core vesicle release, which conferred enhanced starvation survival. This extended survival was reminiscent of that seen in daf-2 insulin-signaling deficient mutants and was ultimately dependent on daf-16, which encodes a FOXO transcription factor whose activity is inhibited by insulin signaling. While insulin signaling modulates metabolism, adult lifespan, and dauer formation, insulin-independent mechanisms that also regulate these processes did not promote starvation survival, indicating that regulation of starvation survival is a distinct program. Cell-specific rescue experiments identified a small subset of primary sensory neurons where unc-31 reconstitution modulated starvation survival, suggesting that these neurons mediate perception of food availability. We found that OCR-2, a transient receptor potential vanilloid (TRPV) channel that localizes to the cilia of this subset of neurons, regulates peptide-hormone secretion and L1 starvation survival. Moreover, inactivation of ocr-2 caused a significant extension in adult lifespan. These findings indicate that TRPV channels, which mediate sensation of diverse noxious, thermal, osmotic, and mechanical stimuli, couple nutrient availability to larval starvation survival and adult lifespan through modulation of neural dense-core vesicle secretion.

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

Temperature °C
23
Diet
Starvation
Lifespan (days)
7.7
Lifespan change (compared to wild type)
-38.40%
Phenotype
Loss of DAF-16/FOXO transcription factor, on L1 starvation survival.
Lifespan comparisons
Double mutant daf-16(mgDf47);unc-31(ft4) has a lifespan of 7.7 days, while single mutant unc-31(ft4) has a lifespan of 26.3 days, single mutant daf-16(mgDf47) has a lifespan of 7.5 days and wild type has a lifespan of 12.5 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Lee BH, Ashrafi K, 2008, A TRPV channel modulates C. elegans neurosecretion, larval starvation survival, and adult lifespan. PLoS Genet. 4(10):e1000213 18846209 Click here to select all mutants from this PubMed ID in the graph
Abstract
For most organisms, food is only intermittently available; therefore, molecular mechanisms that couple sensation of nutrient availability to growth and development are critical for survival. These mechanisms, however, remain poorly defined. In the absence of nutrients, newly hatched first larval (L1) stage Caenorhabditis elegans halt development and survive in this state for several weeks. We isolated mutations in unc-31, encoding a calcium-activated regulator of neural dense-core vesicle release, which conferred enhanced starvation survival. This extended survival was reminiscent of that seen in daf-2 insulin-signaling deficient mutants and was ultimately dependent on daf-16, which encodes a FOXO transcription factor whose activity is inhibited by insulin signaling. While insulin signaling modulates metabolism, adult lifespan, and dauer formation, insulin-independent mechanisms that also regulate these processes did not promote starvation survival, indicating that regulation of starvation survival is a distinct program. Cell-specific rescue experiments identified a small subset of primary sensory neurons where unc-31 reconstitution modulated starvation survival, suggesting that these neurons mediate perception of food availability. We found that OCR-2, a transient receptor potential vanilloid (TRPV) channel that localizes to the cilia of this subset of neurons, regulates peptide-hormone secretion and L1 starvation survival. Moreover, inactivation of ocr-2 caused a significant extension in adult lifespan. These findings indicate that TRPV channels, which mediate sensation of diverse noxious, thermal, osmotic, and mechanical stimuli, couple nutrient availability to larval starvation survival and adult lifespan through modulation of neural dense-core vesicle secretion.

Search genes: daf-16 unc-31

Entrez ID
Symbol
GenAge
Wormbase ID

172981
daf-16
View on GenAge (daf-16)
WBGene00000912

Forkhead box protein O;hypothetical protein

Locus: CELE_R13H8.1

Wormbase description: daf-16 encodes the sole C. elegans forkhead box O (FOXO) homologue; DAF-16 functions as a transcription factor that acts in the insulin/IGF-1-mediated signaling (IIS) pathway that regulates dauer formation, longevity, fat metabolism, stress response, and innate immunity; DAF-16 regulates these various processes through isoform-specific expression, isoform-specific regulation by different AKT kinases, and differential regulation of target genes; DAF-16 can interact with the CBP-1 transcription cofactor in vitro, and interacts genetically with other genes in the insulin signaling and with daf-12, which encodes a nuclear hormone receptor; DAF-16 is activated in response to DNA damage during development and co-regulated by EGL-27, alleviates DNA-damage-induced developmental arrest by inducing DAF-16-associated element (DAE)-regulated genes; DAF-16 is broadly expressed but displays isoform-specific tissue enrichment; DAF-16 localizes to both the cytoplasm and the nucleus, with the ratio between the two an important regulator of function.

Entrez ID
Symbol
GenAge
Wormbase ID

178233
unc-31
View on GenAge (unc-31)
WBGene00006767

Calcium-dependent secretion activator;hypothetical protein

Locus: CELE_ZK897.1

Wormbase description: unc-31 encodes a pleckstrin homology (PH) domain-containing protein that is the C. elegans ortholog of human CADPS/CAPS (calcium-dependent activator protein for secretion OMIM:604667); UNC-31 functions in post-docking calcium-regulated dense-core vesicle fusion that is required for egg laying, locomotion, pharyngeal pumping, and recovery from the dauer larval stage; in addition, UNC-31 functions in the insulin receptor signaling pathway that regulates adult life span where it may control Ca[2+]-regulated secretion of an insulin-like ligand; UNC-31 is not required for synaptic vesicle exocytosis; unc-31::gfp transcriptional reporters are expressed in most, if not all, neurons, vulval muscles, vulval cells, the spermatheca, and secretory cells such as the uterine UV1 cells; UNC-31::GFP translational fusions localize to neuronal cell bodies, axonal projections and to sites of synaptic contact, consistent with other dense-core vesicle proteins.

Orthologs of daf-16;unc-31 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Cadps;Foxo6
Mus musculus	Cadps2;Foxo6
Mus musculus	Cadps;Foxo1
Mus musculus	Cadps2;Foxo1
Mus musculus	Cadps;Foxo4
Mus musculus	Cadps2;Foxo4
Mus musculus	Cadps;Foxo3
Mus musculus	Cadps2;Foxo3

Orthologs of daf-16 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6
Mus musculus	Foxo1
Mus musculus	Foxo4
Mus musculus	Foxo3

Orthologs of unc-31 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Cadps
Mus musculus	Cadps
Mus musculus	Cadps2