Title: | The endogenous ligand Stunted of the GPCR Methuselah extends lifespan in Drosophila |
Author(s): | Cvejic S; Zhu Z; Felice SJ; Berman Y; Huang XY; |
Address: | "Department of Physiology, Cornell University Weill Medical College, New York, New York 10021, USA" |
ISSN/ISBN: | 1465-7392 (Print) 1465-7392 (Linking) |
Abstract: | "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). These G-protein-coupled receptors (GPCRs) control various physiological functions in evolution from pheromone-induced mating in yeast to cognition in humans. 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 flies. 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" |
Keywords: | Aging/genetics/*metabolism Animals Drosophila Proteins/genetics/isolation & purification/*metabolism Drosophila melanogaster/genetics/*metabolism Ligands Longevity/drug effects/*genetics Oxidative Stress/genetics Peptides/chemistry/pharmacology/physiology; |
Notes: | "MedlineCvejic, Svetlana Zhu, Zheng Felice, Sarah J Berman, Yemiliya Huang, Xin-Yun eng Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. England 2004/05/11 Nat Cell Biol. 2004 Jun; 6(6):540-6. doi: 10.1038/ncb1133. Epub 2004 May 9" |