DAF-21/Hsp90 is required for C. elegans longevity by ensuring DAF-16/FOXO isoform A function
| Autor: | Milán Somogyvári, Eszter Gecse, Csaba Sőti |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Transcriptional Activation Transcription Genetic media_common.quotation_subject Mutant Longevity Regulator lcsh:Medicine chemical and pharmacologic phenomena Biology Article Animals Genetically Modified 03 medical and health sciences RNA interference Animals Protein Isoforms HSP90 Heat-Shock Proteins RNA Messenger RNA Small Interfering Caenorhabditis elegans Caenorhabditis elegans Proteins lcsh:Science Transcription factor media_common Regulation of gene expression Gene knockdown Multidisciplinary fungi lcsh:R Gene Expression Regulation Developmental Forkhead Transcription Factors biology.organism_classification Cell biology 030104 developmental biology RNA Interference lcsh:Q Heat-Shock Response Signal Transduction |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-15 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-30592-6 |
| Popis: | The FOXO transcription factor family is a conserved regulator of longevity and the downstream target of insulin/insulin-like signaling. In Caenorhabditis elegans, the FOXO ortholog DAF-16A and D/F isoforms extend lifespan in daf-2 insulin-like receptor mutants. Here we identify the DAF-21/Hsp90 chaperone as a longevity regulator. We find that reducing DAF-21 capacity by daf-21(RNAi) initiated either at the beginning or at the end of larval development shortens wild-type lifespan. daf-21 knockdown employed from the beginning of larval development also decreases longevity of daf-2 mutant and daf-2 silenced nematodes. daf-16 loss-of-function mitigates the lifespan shortening effect of daf-21 silencing. We demonstrate that DAF-21 specifically promotes daf-2 and heat-shock induced nuclear translocation of DAF-16A as well as the induction of DAF-16A-specific mRNAs, without affecting DAF-16D/F localization and transcriptional function. DAF-21 is dispensable for the stability and nuclear import of DAF-16A, excluding a chaperone-client interaction and suggesting that DAF-21 regulates DAF-16A activation upstream of its cellular traffic. Finally, we show a selective requirement for DAF-21 to extend lifespan of DAF-16A, but not DAF-16D/F, transgenic daf-2 mutant strains. Our findings indicate a spatiotemporal determination of multiple DAF-21 roles in fertility, development and longevity and reveal an isoform-specific regulation of DAF-16 activity. |
| Databáze: | OpenAIRE |
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