daf-16;ifta-2

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Genetic mutants with daf-16, ifta-2 alterations

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

Temperature °C
20
Lifespan (days)
19.95
Lifespan change (compared to wild type)
5.22%
Phenotype
The ifta-2(tm1724);daf-16(mu86) double mutants have a significantly reduced lifespan compared with the ifta-2(tm1724) strain and were similar to the daf-16(mu86) mutants alone. Thus, the ifta-2(tm1724) longevity phenotype is dependent on daf-16 function.
Lifespan comparisons
Double mutant daf-16(mu86);ifta-2(tm1724) has a lifespan of 19.95 days, while single mutant daf-16(mu86) has a lifespan of 20.11 days, single mutant ifta-2(tm1724) has a lifespan of 23.02 days and wild type has a lifespan of 18.96 days.
Type of interaction
See methods
Antagonistic (positive)
Citation
View abstract
Schafer JC et al., 2006, IFTA-2 is a conserved cilia protein involved in pathways regulating longevity and dauer formation in Caenorhabditis elegans. J Cell Sci. 119(Pt 19):4088-100 16968739 Click here to select all mutants from this PubMed ID in the graph
Abstract
Defects in cilia are associated with diseases and developmental abnormalities. Proper cilia function is required for sonic hedgehog and PDGFRalpha signaling in mammals and for insulin-like growth factor (IGF) signaling in Caenorhabditis elegans. However, the role of cilia in these pathways remains unknown. To begin addressing this issue, we are characterizing putative cilia proteins in C. elegans that are predicted to have regulatory rather than structural functions. In this report, we characterized the novel cilia protein T28F3.6 (IFTA-2, intraflagellar transport associated protein 2), which is homologous to the mammalian Rab-like 5 protein. We found that, unlike the intraflagellar transport (IFT) genes, disruption of ifta-2 does not result in overt cilia assembly abnormalities, nor did it cause chemotaxis or osmotic avoidance defects typical of cilia mutants. Rather, ifta-2 null mutants have an extended lifespan phenotype and are defective in dauer formation. Our analysis indicates that these phenotypes result from defects in the DAF-2 (insulin-IGF-1-like) receptor signaling pathway in ciliated sensory neurons. We conclude that IFTA-2 is not a ciliogenic protein but rather is a regulator of specific cilia signaling activities. Interestingly, a mammalian IFTA-2 homolog is also found in cilia, raising the possibility that its function has been conserved during evolution.

Search genes: daf-16 ifta-2

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

189055
ifta-2
View on GenAge (ifta-2)
WBGene00012132

Intraflagellar transport associated protein 2

Locus: CELE_T28F3.6

Wormbase description: ifta-2 encodes a ciliary protein, orthologous to human RABL5, that is required for normally short life span and dauer formation; IFTA-2 is expressed in amphid, labial, and phasmid ciliated sensory neurons; intracellularly, IFTA-2 resides in the bases and axonemes of cilia, colocalizing with DAF-2 and AGE-1; IFTA-2 may be either a cargo or a cargo-docking component of intraflagellar transport (IFT) by the IFT-B complex; ciliary basal localization of IFTA-2 is abolished by a T42N mutation predicted to lock ITFA-2 into an inactive, GDP-bound conformation; ifta-2(tm1724) mutants have abnormally long lifespans and constitutive dauer formation, perhaps because IFTA-2 regulates DAF-2 signalling from ciliated sensory neurons; IFTA-2 is not required for cilium assembly or IFT, nor is it required for chemosensation or osmosensation; the ciliary localization of IFTA-2 is conserved in RABL5; via an X-box in its promoter, ifta-2 is a candidate for direct regulation by DAF-19.

Orthologs of daf-16;ifta-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6;Ift22
Mus musculus	Foxo1;Ift22
Mus musculus	Foxo4;Ift22
Mus musculus	Foxo3;Ift22

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 ifta-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Ift22