Nature communications, 2021-07, Vol.12 (1), p.4568-4568, Article 4568
2021
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- Autor(en) / Beteiligte
- Titel
- Insulin signaling regulates longevity through protein phosphorylation in Caenorhabditis elegans
- Ist Teil von
- Nature communications, 2021-07, Vol.12 (1), p.4568-4568, Article 4568
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Insulin/IGF-1 Signaling (IIS) is known to constrain longevity by inhibiting the transcription factor FOXO. How phosphorylation mediated by IIS kinases regulates lifespan beyond FOXO remains unclear. Here, we profile IIS-dependent phosphorylation changes in a large-scale quantitative phosphoproteomic analysis of wild-type and three IIS mutant Caenorhabditis elegans strains. We quantify more than 15,000 phosphosites and find that 476 of these are differentially phosphorylated in the long-lived daf-2/insulin receptor mutant. We develop a machine learning-based method to prioritize 25 potential lifespan-related phosphosites. We perform validations to show that AKT-1 pT492 inhibits DAF-16/FOXO and compensates the loss of daf-2 function, that EIF-2α pS49 potently inhibits protein synthesis and daf-2 longevity, and that reduced phosphorylation of multiple germline proteins apparently transmits reduced DAF-2 signaling to the soma. In addition, an analysis of kinases with enriched substrates detects that casein kinase 2 (CK2) subunits negatively regulate lifespan. Our study reveals detailed functional insights into longevity.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-021-24816-zTitel-ID: cdi_doaj_primary_oai_doaj_org_article_79b32e5ef67f4e64b5c54680fd9b724a
- Format
- –
- Schlagworte
- AKT protein, AKT1 protein, Algorithms, Amino Acid Sequence, Animals, Caenorhabditis elegans, Caenorhabditis elegans - physiology, Caenorhabditis elegans Proteins - chemistry, Caenorhabditis elegans Proteins - metabolism, Casein, Casein kinase II, Forkhead protein, Germ Cells - metabolism, Humans, Insulin, Insulin - metabolism, Insulin-like growth factor I, Insulin-Like Growth Factor I - metabolism, Kinases, Learning algorithms, Life span, Longevity, Longevity - physiology, Machine learning, Models, Biological, Mutants, Mutation - genetics, Nematodes, Phosphoproteins - metabolism, Phosphorylation, Protein biosynthesis, Protein synthesis, Proteins, Proteome - metabolism, Proteomics, Signal Transduction, Signaling, Substrates