IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-25920-w.html
   My bibliography  Save this article

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

Author

Listed:
  • Hae-Eun H. Park

    (Korea Advanced Institute of Science and Technology)

  • Wooseon Hwang

    (Pohang University of Science and Technology)

  • Seokjin Ham

    (Korea Advanced Institute of Science and Technology)

  • Eunah Kim

    (Korea Advanced Institute of Science and Technology)

  • Ozlem Altintas

    (Pohang University of Science and Technology)

  • Sangsoon Park

    (Korea Advanced Institute of Science and Technology)

  • Heehwa G. Son

    (Korea Advanced Institute of Science and Technology)

  • Yujin Lee

    (Korea Advanced Institute of Science and Technology)

  • Dongyeop Lee

    (Pohang University of Science and Technology)

  • Won Do Heo

    (Korea Advanced Institute of Science and Technology)

  • Seung-Jae V. Lee

    (Korea Advanced Institute of Science and Technology)

Abstract

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.

Suggested Citation

  • Hae-Eun H. Park & Wooseon Hwang & Seokjin Ham & Eunah Kim & Ozlem Altintas & Sangsoon Park & Heehwa G. Son & Yujin Lee & Dongyeop Lee & Won Do Heo & Seung-Jae V. Lee, 2021. "A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25920-w
    DOI: 10.1038/s41467-021-25920-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-25920-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-25920-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25920-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.