Letter abstract
Nature Cell Biology 10, 468 - 475 (2008)
Published online: 16 March 2008 | doi:10.1038/ncb1710
Drosophila short neuropeptide F signalling regulates growth by ERK-mediated insulin signalling
Kyu-Sun Lee1,6, O-Yu Kwon2,6, Joon H. Lee3,6, Kisang Kwon2, Kyung-Jin Min4,7, Sun-Ah Jung3, Ae-Kyeong Kim1, Kwan-Hee You5, Marc Tatar4 & Kweon Yu1
Insulin and insulin growth factor have central roles in growth1, 2, metabolism3 and ageing4, 5 of animals, including Drosophila melanogaster. In Drosophila, insulin-like peptides (Dilps) are produced by specialized neurons in the brain3, 6. Here we show that Drosophila short neuropeptide F (sNPF), an orthologue of mammalian neuropeptide Y (NPY), and sNPF receptor sNPFR1 regulate expression of Dilps. Body size was increased by overexpression of sNPF or sNPFR1. The fat body of sNPF mutant Drosophila had downregulated Akt, nuclear localized FOXO, upregulated translational inhibitor 4E-BP and reduced cell size. Circulating levels of glucose were elevated and lifespan was also extended in sNPF mutants. We show that these effects are mediated through activation of extracellular signal-related kinases (ERK) in insulin-producing cells of larvae and adults. Insulin expression was also increased in an ERK-dependent manner in cultured Drosophila central nervous system (CNS) cells and in rat pancreatic cells treated with sNPF or NPY peptide, respectively. Drosophila sNPF and the evolutionarily conserved mammalian NPY seem to regulate ERK-mediated insulin expression and thus to systemically modulate growth, metabolism and lifespan.
- Centre for Regenerative Medicine, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-333, Korea.
- Department of Anatomy, College of Medicine, Chungnam National University, Daejeon, Korea.
- Myung-Gok Eye Research Institute, Kim's Eye Hospital, College of Medicine, Konyang University, Chungnam, Korea.
- Department of Ecology and Evolutionary Biology, Brown University, Providence, RI 02912, USA.
- School of Bioscience and Biotechnology, Chungnam National University, Daejeon, Korea.
- These authors contributed equally to this work.
- Present address: Department of Biological Sciences, University of Alaska at Anchorage, Anchorage, AK 99508, USA.
Correspondence to: Kweon Yu1 e-mail: kweonyu@kribb.re.kr
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