한빛사논문
- 조회719
Hae-Eun H. Park1,4, Wooseon Hwang2,4, Seokjin Ham1,4, Eunah Kim1,4, Ozlem Altintas3, Sangsoon Park1, Heehwa G. Son1, Yujin Lee1, Dongyeop Lee2, Won Do Heo1 & Seung-Jae V. Lee1,*
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, South Korea. 2Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, South Korea. 3School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang 37673, South Korea. 4These authors contributed equally: Hae-Eun H. Park, Wooseon Hwang, Seokjin Ham, Eunah Kim.
*Corresponding author.
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.
논문정보
- Research article
- 2021년 09월 (BRIC 등록일 2021-09-29)
- 국내 연구진
- 생명과학 > 노화/암생물학
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