daf-2;ifta-2

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Genetic mutants with daf-2, ifta-2 alterations

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

Temperature °C
20
Lifespan (days)
24.64
Lifespan change (compared to wild type)
47.81%
Phenotype
We compared the lifespan of daf-2(e1370) mutants, ifta-2(tm1724) mutants and daf-2(e1370);ifta-2(tm1724) double mutants, and found that lifespans of all three are not statistically different.
Lifespan comparisons
Double mutant daf-2(e1370);ifta-2(tm1724) has a lifespan of 24.64 days, while single mutant daf-2(e1370) has a lifespan of 24.01 days, single mutant ifta-2(tm1724) has a lifespan of 23.26 days and wild type has a lifespan of 16.67 days.
Type of interaction
See methods
Almost additive (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-2 ifta-2

Entrez ID
Symbol
GenAge
Wormbase ID

175410
daf-2
View on GenAge (daf-2)
WBGene00000898

Insulin-like receptor subunit beta;Receptor protein-tyrosine kinase;hypothetical protein

Locus: CELE_Y55D5A.5

Wormbase description: daf-2 encodes a receptor tyrosine kinase that is the C. elegans insulin/IGF receptor ortholog; DAF-2 activity is required for a number of processes in C. elegans, including embryonic and larval development, formation of the developmentally arrested dauer larval stage (diapause), larval developmental timing, adult longevity, reproduction, fat storage, salt chemotaxis learning, and stress resistance, including response to high temperature, oxidative stress, and bacterial infection; DAF-2 signals through a conserved PI 3-kinase pathway to negatively regulate the activity of DAF-16, a Forkhead-related transcription factor, by inducing its phosphorylation and nuclear exclusion; in addition, DAF-2 negatively regulates the nuclear localization, and hence transcriptional activity, of SKN-1 in intestinal nuclei; amongst the 38 predicted insulin-like molecules in C. elegans, genetic and microarray analyses suggest that at least DAF-28, INS-1, and INS-7 are likely DAF-2 ligands; genetic mosaic and tissue-specific promoter studies indicate that daf-2 can function cell nonautonomously and within multiple cell types to influence dauer formation and adult lifespan, likely by regulating the production of secondary endocrine signals that coordinate growth and longevity throughout the animal; temporal analysis of daf-2 function indicates that daf-2 regulates lifespan, reproduction, and diapause independently, at distinct times during the animal's life cycle.

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-2;ifta-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Ift22;Insr
Mus musculus	Ift22;Igf1r
Mus musculus	Ift22;Insrr
Mus musculus	Insr;Ift22
Mus musculus	Igf1r;Ift22
Mus musculus	Insrr;Ift22

Orthologs of daf-2 in SynergyAge

Show in SynergyAge
Species	Gene
Drosophila melanogaster	InR

Not in SynergyAge
Species	Gene
Mus musculus	Insr
Mus musculus	Igf1r
Mus musculus	Insrr

Orthologs of ifta-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Ift22