ddr-2;rab-10

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Genetic mutants with ddr-2, rab-10 alterations

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

Temperature °C
20
Lifespan (days)
18.39
Lifespan change (compared to wild type)
6.79%
Phenotype
Inhibition of rab-10 by RNAi does not extend the lifespan of EQ19 (drr-2 over-expression) significantly, while inhibition of rab-10 xtends the lifespan of wild-type animals, suggesting a common mechanism that mediates the lifespan effects of eIF4H/drr-2 and rab-10.
Lifespan comparisons
Double mutant ddr-2(OE);rab-10(RNAi) has a lifespan of 18.39 days, while single mutant rab-10(RNAi) has a lifespan of 23.9 days, single mutant ddr-2(OE) has a lifespan of 17.14 days and wild type has a lifespan of 17.22 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Ching TT et al., 2010, drr-2 encodes an eIF4H that acts downstream of TOR in diet-restriction-induced longevity of C. elegans. Aging Cell. 9(4):545-57 20456299 Click here to select all mutants from this PubMed ID in the graph
Abstract
Dietary restriction (DR) results in a robust increase in lifespan while maintaining the physiology of much younger animals in a wide range of species. Here, we examine the role of drr-2, a DR-responsive gene recently identified, in determining the longevity of Caenorhabditis elegans. Inhibition of drr-2 has been shown to increase longevity. However, the molecular mechanisms by which drr-2 influences longevity remain unknown. We report here that drr-2 encodes an ortholog of human eukaryotic translation initiation factor 4H (eIF4H), whose function is to mediate the initiation step of mRNA translation. The molecular function of DRR-2 is validated by the association of DRR-2 with polysomes and by the decreased rate of protein synthesis observed in drr-2 knockdown animals. Previous studies have also suggested that DR might trigger a regulated reduction in drr-2 expression to initiate its longevity response. By examining the effect of increasing drr-2 expression on DR animals, we find that drr-2 is essential for a large portion of the longevity response to DR. The nutrient-sensing target of rapamycin (TOR) pathway has been shown to mediate the longevity effects of DR in C. elegans. Results from our genetic analyses suggest that eIF4H/DRR-2 functions downstream of TOR, but in parallel to the S6K/PHA-4 pathway to mediate the lifespan effects of DR. Together, our findings reveal an important role for eIF4H/drr-2 in the TOR-mediated longevity responses to DR.

Temperature °C
20
Lifespan (days)
18.75
Lifespan change (compared to wild type)
13.22%
Phenotype
Inhibition of rab-10 by RNAi does not extend the lifespan of EQ19 (drr-2 over-expression) significantly, while inhibition of rab-10 xtends the lifespan of wild-type animals, suggesting a common mechanism that mediates the lifespan effects of eIF4H/drr-2 and rab-10.
Lifespan comparisons
Double mutant ddr-2(OE);rab-10(RNAi) has a lifespan of 18.75 days, while single mutant rab-10(RNAi) has a lifespan of 20.0 days, single mutant ddr-2(OE) has a lifespan of 17.06 days and wild type has a lifespan of 16.56 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Ching TT et al., 2010, drr-2 encodes an eIF4H that acts downstream of TOR in diet-restriction-induced longevity of C. elegans. Aging Cell. 9(4):545-57 20456299 Click here to select all mutants from this PubMed ID in the graph
Abstract
Dietary restriction (DR) results in a robust increase in lifespan while maintaining the physiology of much younger animals in a wide range of species. Here, we examine the role of drr-2, a DR-responsive gene recently identified, in determining the longevity of Caenorhabditis elegans. Inhibition of drr-2 has been shown to increase longevity. However, the molecular mechanisms by which drr-2 influences longevity remain unknown. We report here that drr-2 encodes an ortholog of human eukaryotic translation initiation factor 4H (eIF4H), whose function is to mediate the initiation step of mRNA translation. The molecular function of DRR-2 is validated by the association of DRR-2 with polysomes and by the decreased rate of protein synthesis observed in drr-2 knockdown animals. Previous studies have also suggested that DR might trigger a regulated reduction in drr-2 expression to initiate its longevity response. By examining the effect of increasing drr-2 expression on DR animals, we find that drr-2 is essential for a large portion of the longevity response to DR. The nutrient-sensing target of rapamycin (TOR) pathway has been shown to mediate the longevity effects of DR in C. elegans. Results from our genetic analyses suggest that eIF4H/DRR-2 functions downstream of TOR, but in parallel to the S6K/PHA-4 pathway to mediate the lifespan effects of DR. Together, our findings reveal an important role for eIF4H/drr-2 in the TOR-mediated longevity responses to DR.

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

Temperature °C
20
Lifespan (days)
20.86
Lifespan change (compared to wild type)
11.19%
Phenotype
Inhibition of eIF4H/drr-2 consistently extends the lifespan of wild-type animals and animals over-expressing rab-10 (EQ28). Taken together, these results strongly imply that eIF4H/drr-2 may act downstream of both rab-10 and sams-1 and its activity might be essential for RAB-10 and SAMS-1 to mediate the longevity effects of DR.
Lifespan comparisons
Double mutant ddr-2(RNAi);rab-10(OE) has a lifespan of 20.86 days, while single mutant ddr-2(RNAi) has a lifespan of 22.15 days, single mutant rab-10(OE) has a lifespan of 16.59 days and wild type has a lifespan of 18.76 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Ching TT et al., 2010, drr-2 encodes an eIF4H that acts downstream of TOR in diet-restriction-induced longevity of C. elegans. Aging Cell. 9(4):545-57 20456299 Click here to select all mutants from this PubMed ID in the graph
Abstract
Dietary restriction (DR) results in a robust increase in lifespan while maintaining the physiology of much younger animals in a wide range of species. Here, we examine the role of drr-2, a DR-responsive gene recently identified, in determining the longevity of Caenorhabditis elegans. Inhibition of drr-2 has been shown to increase longevity. However, the molecular mechanisms by which drr-2 influences longevity remain unknown. We report here that drr-2 encodes an ortholog of human eukaryotic translation initiation factor 4H (eIF4H), whose function is to mediate the initiation step of mRNA translation. The molecular function of DRR-2 is validated by the association of DRR-2 with polysomes and by the decreased rate of protein synthesis observed in drr-2 knockdown animals. Previous studies have also suggested that DR might trigger a regulated reduction in drr-2 expression to initiate its longevity response. By examining the effect of increasing drr-2 expression on DR animals, we find that drr-2 is essential for a large portion of the longevity response to DR. The nutrient-sensing target of rapamycin (TOR) pathway has been shown to mediate the longevity effects of DR in C. elegans. Results from our genetic analyses suggest that eIF4H/DRR-2 functions downstream of TOR, but in parallel to the S6K/PHA-4 pathway to mediate the lifespan effects of DR. Together, our findings reveal an important role for eIF4H/drr-2 in the TOR-mediated longevity responses to DR.

Temperature °C
20
Lifespan (days)
20.37
Lifespan change (compared to wild type)
-6.04%
Phenotype
Inhibition of eIF4H/drr-2 consistently extends the lifespan of wild-type animals and animals over-expressing rab-10 (EQ28). Taken together, these results strongly imply that eIF4H/drr-2 may act downstream of both rab-10 and sams-1 and its activity might be essential for RAB-10 and SAMS-1 to mediate the longevity effects of DR.
Lifespan comparisons
Double mutant ddr-2(RNAi);rab-10(OE) has a lifespan of 20.37 days, while single mutant ddr-2(RNAi) has a lifespan of 25.2 days, single mutant rab-10(OE) has a lifespan of 17.98 days and wild type has a lifespan of 21.68 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Ching TT et al., 2010, drr-2 encodes an eIF4H that acts downstream of TOR in diet-restriction-induced longevity of C. elegans. Aging Cell. 9(4):545-57 20456299 Click here to select all mutants from this PubMed ID in the graph
Abstract
Dietary restriction (DR) results in a robust increase in lifespan while maintaining the physiology of much younger animals in a wide range of species. Here, we examine the role of drr-2, a DR-responsive gene recently identified, in determining the longevity of Caenorhabditis elegans. Inhibition of drr-2 has been shown to increase longevity. However, the molecular mechanisms by which drr-2 influences longevity remain unknown. We report here that drr-2 encodes an ortholog of human eukaryotic translation initiation factor 4H (eIF4H), whose function is to mediate the initiation step of mRNA translation. The molecular function of DRR-2 is validated by the association of DRR-2 with polysomes and by the decreased rate of protein synthesis observed in drr-2 knockdown animals. Previous studies have also suggested that DR might trigger a regulated reduction in drr-2 expression to initiate its longevity response. By examining the effect of increasing drr-2 expression on DR animals, we find that drr-2 is essential for a large portion of the longevity response to DR. The nutrient-sensing target of rapamycin (TOR) pathway has been shown to mediate the longevity effects of DR in C. elegans. Results from our genetic analyses suggest that eIF4H/DRR-2 functions downstream of TOR, but in parallel to the S6K/PHA-4 pathway to mediate the lifespan effects of DR. Together, our findings reveal an important role for eIF4H/drr-2 in the TOR-mediated longevity responses to DR.

Search genes: ddr-2 rab-10

Entrez ID
Symbol
GenAge
Wormbase ID

180622
ddr-2
View on GenAge (ddr-2)
WBGene00017381

Discoidin domain-containing receptor tyrosine kinase B

Locus: CELE_F11D5.3

Wormbase description: F11D5.3 encodes a putative tyrosine kinase homologous to human RS1 (OMIM:312700, mutated in juvenile X-linked retinoschisis).

Entrez ID
Symbol
GenAge
Wormbase ID

266836
rab-10
View on GenAge (rab-10)
WBGene00004273

Ras-related protein Rab-10

Locus: CELE_T23H2.5

Wormbase description: rab-10 encodes a Rab-like GTPase that is a member of the Ras superfamily of small GTPases; RAB-10 is required, upstream of RME-1, for basolateral endocytic recycling in the intestine, but not in oocytes or coelomocytes; RAB-10 is also required for GLR-1 receptor recycling in interneurons; a RAB-10::GFP fusion protein is widely expressed and in the intestine, localizes to early endosomes and the Golgi.

Orthologs of ddr-2;rab-10 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Ddr1;Rab10
Mus musculus	Ddr2;Rab10
Mus musculus	Rab10;Ddr1
Mus musculus	Rab10;Ddr2

Orthologs of ddr-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Ddr1
Mus musculus	Ddr2

Orthologs of rab-10 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Rab10
Mus musculus	Rab10