論文 - 詳細
| RRC ID | 76309 |
|---|---|
| 著者 | Traa A, Soo SK, AlOkda A, Ko B, Rocheleau CE, Van Raamsdonk JM. |
| タイトル | Endosomal trafficking protein TBC-2 modulates stress resistance and lifespan through DAF-16-dependent and independent mechanisms. |
| ジャーナル | Aging Cell |
| 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. |
| 巻・号 | 22(3) |
| ページ | e13762 |
| 公開日 | 2023-3-1 |
| DOI | 10.1111/acel.13762 |
| PMID | 36794357 |
| PMC | PMC10014066 |
| MeSH | Animals Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Forkhead Transcription Factors / genetics Forkhead Transcription Factors / metabolism GTPase-Activating Proteins / metabolism Insulin / metabolism Longevity* / genetics Transcription Factors / metabolism |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.2 |
| リソース情報 | |
| 線虫 | tm2241 |