ArticleAging cell2023
Endosomal trafficking protein TBC-2 modulates stress resistance and lifespan through DAF-16-dependent and independent mechanisms.
Article in Aging cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- Multilayered regulation of longevity in Caenorhabditis elegans.Molecules and cells · 2026Review
- Endosomal catabolism of phosphatidylinositol 4,5-bisphosphate is fundamental in building resilience against pathogens.Protein & cell · 2025Article
- Endosomal trafficking protein TBC-2 modulates stress resistance and lifespan through DAF-16-dependent and independent mechanisms.Aging cell · 2023Article
- Endosomal trafficking protein TBC-2 is required for the longevity of long-lived mitochondrial mutants.Frontiers in aging · 2023Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The FOXO transcription factor, DAF-16, plays an integral role in insulin/IGF-1 signaling (IIS) and stress response. In conditions of stress or decreased IIS, DAF-16 moves to the nucleus where it activates genes that promote survival. To gain insight into the role of endosomal trafficking in resistance to stress, we disrupted tbc-2, which encodes a GTPase activating protein that inhibits RAB-5 and RAB-7. We found that tbc-2 mutants have decreased nuclear localization of DAF-16 in response to heat stress, anoxia, and bacterial pathogen stress, but increased nuclear localization of DAF-16 in response to chronic oxidative stress and osmotic stress. tbc-2 mutants also exhibit decreased upregulation of DAF-16 target genes in response to stress. To determine whether the rate of nuclear localization of DAF-16 affected stress resistance in these animals, we examined survival after exposure to multiple exogenous stressors. Disruption of tbc-2 decreased resistance to heat stress, anoxia, and bacterial pathogen stress in both wild-type worms and stress-resistant daf-2 insulin/IGF-1 receptor mutants. Similarly, deletion of tbc-2 decreases lifespan in both wild-type worms and daf-2 mutants. When DAF-16 is absent, the loss of tbc-2 is still able to decrease lifespan but has little or no impact on resistance to most stresses. Combined, this suggests that disruption of tbc-2 affects lifespan through both DAF-16-dependent and DAF-16-independent pathways, while the effect of tbc-2 deletion on resistance to stress is primarily DAF-16-dependent. Overall, this work demonstrates the importance of endosomal trafficking for the proper nuclear localization of DAF-16 during stress and that perturbation of normal endosomal trafficking is sufficient to decrease both stress resistance and lifespan.
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