期刊论文详细信息
Aging Cell
Modulation of methuselah expression targeted to Drosophila insulin‐producing cells extends life and enhances oxidative stress resistance
Luis E. D. Gimenez2  Parakashtha Ghildyal2  Kathleen E. Fischer4  Hongxiang Hu2  William W. Ja1  Benjamin A. Eaton4  Yimin Wu4  Steven N. Austad3 
[1] Department of Metabolism & Aging, The Scripps Research Institute, Jupiter, FL, USA;Department of Pharmacology, University of Texas Health Science Center San Antonio, San Antonio, TX, USA;Department of Cellular & Structural Biology and Department of Molecular Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX, USA;Department of Physiology, University of Texas Health Science Center San Antonio, San Antonio, TX, USA
关键词: aging;    Drosophila;    endocrinology;    genetics;    insulin/IGF‐1signaling;    longevity;    neuroscience;    signaling;   
DOI  :  10.1111/acel.12027
来源: Wiley
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【 摘 要 】

Summary

Ubiquitously reduced signaling via Methuselah (MTH), a G-protein-coupled receptor (GPCR) required for neurosecretion, has previously been reported to extend life and enhance stress resistance in flies. Whether these effects are due to reduced MTH signalling in specific tissues remains unknown. We determined that reduced expression of mth targeted to the insulin-producing cells (IPCs) of the fly brain was sufficient to extend life and enhance oxidative stress resistance. Paradoxically, we discovered that overexpression of mth targeted to the same cells has similar phenotypic effects to reduced expression due to MTH's interaction with β-arrestin, which uncouples GPCRs from their G-proteins. We confirmed the functional relationship between MTH and β-arrestin by finding that IPC-targeted overexpression of β-arrestin alone mimics the longevity phenotype of reduced MTH signaling. As reduced MTH signaling also inhibits insulin secretion from the IPCs, the most parsimonious mechanistic explanation of its longevity and stress-resistance enhancement might be through reduced insulin/IGF signaling (IIS). However, examination of phenotypic features of long-lived IPC-mth modulated flies as well as several downstream IIS targets implicates enhanced activity of the JNK stress-resistance pathway more directly than insulin signaling in the longevity and stress-resistance phenotypes.

【 授权许可】

Unknown   
© 2012 The Authors Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland

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