A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling

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...

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Autores principales: Park, Hae-Eun H., Hwang, Wooseon, Ham, Seokjin, Kim, Eunah, Altintas, Ozlem, Park, Sangsoon, Son, Heehwa G., Lee, Yujin, Lee, Dongyeop, Heo, Won Do, Lee, Seung-Jae V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463539/
https://www.ncbi.nlm.nih.gov/pubmed/34561453
http://dx.doi.org/10.1038/s41467-021-25920-w
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author Park, Hae-Eun H.
Hwang, Wooseon
Ham, Seokjin
Kim, Eunah
Altintas, Ozlem
Park, Sangsoon
Son, Heehwa G.
Lee, Yujin
Lee, Dongyeop
Heo, Won Do
Lee, Seung-Jae V.
author_facet Park, Hae-Eun H.
Hwang, Wooseon
Ham, Seokjin
Kim, Eunah
Altintas, Ozlem
Park, Sangsoon
Son, Heehwa G.
Lee, Yujin
Lee, Dongyeop
Heo, Won Do
Lee, Seung-Jae V.
author_sort Park, Hae-Eun H.
collection PubMed
description 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.
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spelling pubmed-84635392021-10-22 A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling Park, Hae-Eun H. Hwang, Wooseon Ham, Seokjin Kim, Eunah Altintas, Ozlem Park, Sangsoon Son, Heehwa G. Lee, Yujin Lee, Dongyeop Heo, Won Do Lee, Seung-Jae V. Nat Commun Article 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. Nature Publishing Group UK 2021-09-24 /pmc/articles/PMC8463539/ /pubmed/34561453 http://dx.doi.org/10.1038/s41467-021-25920-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Park, Hae-Eun H.
Hwang, Wooseon
Ham, Seokjin
Kim, Eunah
Altintas, Ozlem
Park, Sangsoon
Son, Heehwa G.
Lee, Yujin
Lee, Dongyeop
Heo, Won Do
Lee, Seung-Jae V.
A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling
title A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling
title_full A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling
title_fullStr A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling
title_full_unstemmed A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling
title_short A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling
title_sort pten variant uncouples longevity from impaired fitness in caenorhabditis elegans with reduced insulin/igf-1 signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463539/
https://www.ncbi.nlm.nih.gov/pubmed/34561453
http://dx.doi.org/10.1038/s41467-021-25920-w
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