Letter abstract
Nature Cell Biology 6, 540 - 546 (2004)
Published online: 9 May 2004 | doi:10.1038/ncb1133
The endogenous ligand Stunted of the GPCR Methuselah extends lifespan in Drosophila
Svetlana Cvejic1, Zheng Zhu1, Sarah J. Felice1, Yemiliya Berman2 & Xin-Yun Huang1
Many extracellular signals are transmitted to the interior of the cell by receptors with seven membrane-spanning helices that trigger their effects by means of heterotrimeric guanine-nucleotide-binding regulatory proteins (G proteins)1, 2, 3, 4. These G-protein-coupled receptors (GPCRs) control various physiological functions in evolution from pheromone-induced mating in yeast to cognition in humans5, 6. The potential role of the G-protein signalling system in the control of animal ageing has been highlighted by the genetic revelation that mutation of a GPCR encoded by methuselah extends the lifespan of adult Drosophila flies7. How methuselah functions in controlling ageing is not clear. A first essential step towards the understanding of methuselah function is to determine the ligands of Methuselah. Here we report the identification and characterization of two endogenous peptide ligands of Methuselah, designated Stunted A and B. Flies with mutations in the gene encoding these ligands show an increase in lifespan and resistance to oxidative stress. We conclude that the Stunted–Methuselah system is involved in the control of animal ageing.
- Department of Physiology, Cornell University Weill Medical College, New York, New York 10021, USA.
- Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA.
Correspondence to: Xin-Yun Huang1 e-mail: xyhuang@med.cornell.edu
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