A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling
| Autor: | Yujin Lee, Ozlem Altintas, Seokjin Ham, Eunah Kim, Seung-Jae Lee, Won Do Heo, Hae-Eun H. Park, Wooseon Hwang, Dongyeop Lee, Sangsoon Park, Heehwa G. Son |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_treatment
animal diseases Science Green Fluorescent Proteins Longevity General Physics and Astronomy Motility chemical and pharmacologic phenomena Development medicine.disease_cause General Biochemistry Genetics and Molecular Biology Article Receptor IGF Type 1 Animals Genetically Modified Downregulation and upregulation medicine PTEN Animals RNA-Seq Caenorhabditis elegans Caenorhabditis elegans Proteins Mutation Multidisciplinary biology Insulin fungi PTEN Phosphohydrolase Forkhead Transcription Factors General Chemistry biochemical phenomena metabolism and nutrition biology.organism_classification Receptor Insulin Cell biology Ageing Microscopy Fluorescence Lipid phosphatase activity biology.protein bacteria Genetic Fitness Signal transduction |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Insulin/IGF-1 signaling (IIS) regulates various physiological aspects in numerous species. In Caenorhabditis elegans, mutations in the daf-2/insulin/IGF-1 receptor dramatically increase lifespan and immunity, but generally impair motility, growth, and reproduction. Whether these pleiotropic effects can be dissociated at a specific step in insulin/IGF-1 signaling pathway remains unknown. Through performing a mutagenesis screen, we identified a missense mutation daf-18(yh1) that alters a cysteine to tyrosine in DAF-18/PTEN phosphatase, which maintained the long lifespan and enhanced immunity, while improving the reduced motility in adult daf-2 mutants. We showed that the daf-18(yh1) mutation decreased the lipid phosphatase activity of DAF-18/PTEN, while retaining a partial protein tyrosine phosphatase activity. We found that daf-18(yh1) maintained the partial activity of DAF-16/FOXO but restricted the detrimental upregulation of SKN-1/NRF2, contributing to beneficial physiological traits in daf-2 mutants. Our work provides important insights into how one evolutionarily conserved component, PTEN, can coordinate animal health and longevity. Mutations in daf-2/insulin/IGF-1 receptor impair the growth and reproduction of C. elegans but conversely enhance immunity and lifespan. Here, the authors show that a missense mutation in the gene retains the effects on lifespan and immunity and improves motility. |
| Databáze: | OpenAIRE |
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