Feeding behavior is one of the most essential activities in animals, which is tightly regulated by neuroendocrine factors. Drosophila melanogaster short neuropeptide F (sNPF) and the mammalian functional homolog neuropeptide Y (NPY) regulate food intake. Understanding the molecular mechanism of sNPF and NPY signaling is critical to elucidate feeding regulation. Here, we found that minibrain (mnb) and the mammalian ortholog Dyrk1a target genes of sNPF and NPY signaling and regulate food intake in Drosophila melanogaster and mice. In Drosophila melanogaster neuronal cells and mouse hypothalamic cells, sNPF and NPY modulated the mnb and Dyrk1a expression through the PKA-CREB pathway. Increased Dyrk1a activated Sirt1 to regulate the deacetylation of FOXO, which potentiated FOXO-induced sNPF/NPY expression and in turn promoted food intake. Conversely, AKT-mediated insulin signaling suppressed FOXO-mediated sNPF/NPY expression, which resulted in decreasing food intake. Furthermore, human Dyrk1a transgenic mice exhibited decreased FOXO acetylation and increased NPY expression in the hypothalamus, as well as increased food intake. Our findings demonstrate that Mnb/Dyrk1a regulates food intake through the evolutionary conserved Sir2-FOXO-sNPF/NPY pathway in Drosophila melanogaster and mammals.
Vyšlo v časopise: Minibrain/Dyrk1a Regulates Food Intake through the Sir2-FOXO-sNPF/NPY Pathway in and Mammals. PLoS Genet 8(8): e32767. doi:10.1371/journal.pgen.1002857 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002857
1. MortonGJCummingsDEBaskinDGBarshGSSchwartzMW 2006 Central nervous system control of food intake and body weight. Nature 443 289 295
2. LeeKSYouKHChooJKHanYMYuK 2004 Drosophila short neuropeptide F regulates food intake and body size. J Biol Chem 279 50781 50789
3. LeeKSKwonOYLeeJHKwonKMinKJ 2008 Drosophila short neuropeptide F signalling regulates growth by ERK-mediated insulin signalling. Nat Cell Biol 10 468 475
4. GuimeraJCasasCEstivillXPritchardM 1999 Human minibrain homologue (MNBH/DYRK1): characterization, alternative splicing, differential tissue expression, and overexpression in Down syndrome. Genomics 57 407 418
5. GuimeraJCasasCPucharcosCSolansADomenechA 1996 A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal regions affected in Down syndrome and maps to the critical region. Hum Mol Genet 5 1305 1310
6. TejedorFZhuXRKaltenbachEAckermannABaumannA 1995 minibrain: a new protein kinase family involved in postembryonic neurogenesis in Drosophila. Neuron 14 287 301
7. SongWJSternbergLRKasten-SportesCKeurenMLChungSH 1996 Isolation of human and murine homologues of the Drosophila minibrain gene: human homologue maps to 21q22.2 in the Down syndrome “critical region” Genomics 38 331 339
8. DowjatWKAdayevTKuchnaINowickiKPalminielloS 2007 Trisomy-driven overexpression of DYRK1A kinase in the brain of subjects with Down syndrome. Neurosci Lett 413 77 81
9. FotakiVDierssenMAlcantaraSMartinezSMartiE 2002 Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in mice. Mol Cell Biol 22 6636 6647
10. MollerRSKubartSHoeltzenbeinMHeyeBVogelI 2008 Truncation of the Down syndrome candidate gene DYRK1A in two unrelated patients with microcephaly. Am J Hum Genet 82 1165 1170
11. van BonBWHoischenAHehir-KwaJde BrouwerAPRuivenkampC 2011 Intragenic deletion in DYRK1A leads to mental retardation and primary microcephaly. Clinical Genetics 79 296 299
12. KitamuraTFengYKitamuraYIChuaSCJrXuAW 2006 Forkhead protein FoxO1 mediates Agrp-dependent effects of leptin on food intake. Nat Med 12 534 540
13. RamadoriGLeeCEBookoutALLeeSWilliamsKW 2008 Brain SIRT1: anatomical distribution and regulation by energy availability. J Neurosci 28 9989 9996
14. DietrichMOAntunesCGeliangGLiuZWBorokE 2010 Agrp neurons mediate Sirt1's action on the melanocortin system and energy balance: roles for Sirt1 in neuronal firing and synaptic plasticity. J Neurosci 30 11815 11825
15. CakirIPerelloMLansariOMessierNJVasletCA 2009 Hypothalamic Sirt1 regulates food intake in a rodent model system. PLoS ONE 4 e8322 doi:10.1371/journal.pone.0008322
16. LeeKSHongSHKimAKJuSKKwonOY 2009 Processed short neuropeptide F peptides regulate growth through the ERK-insulin pathway in Drosophila melanogaster. FEBS Lett 583 2573 2577
17. JaWWCarvalhoGBMakEMde la RosaNNFangAY 2007 Prandiology of Drosophila and the CAFE assay. Proc Natl Acad Sci U S A 104 8253 8256
18. McGuireSEMaoZDavisRL 2004 Spatiotemporal gene expression targeting with the TARGET and gene-switch systems in Drosophila. Sci STKE 2004 pl6
19. UiKNishiharaSSakumaMTogashiSUedaR 1994 Newly established cell lines from Drosophila larval CNS express neural specific characteristics. In Vitro Cellular and Developmental Biology Animal 30A 209 216
20. RitterSLHallRA 2009 Fine-tuning of GPCR activity by receptor-interacting proteins. Nat Rev Mol Cell Biol 10 819 830
21. MayrBMontminyM 2001 Transcriptional regulation by the phosphorylation-dependent factor CREB. Nat Rev Mol Cell Biol 2 599 609
22. MellonPLWindleJJGoldsmithPCPadulaCARobertsJL 1990 Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis. Neuron 5 1 10
23. BlomqvistAGHerzogH 1997 Y-receptor subtypes–how many more? Trends Neurosci 20 294 298
24. KamijiMMInuiA 2007 Neuropeptide y receptor selective ligands in the treatment of obesity. Endocr Rev 28 664 684
25. ZhangXOdomDTKooSHConkrightMDCanettieriG 2005 Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues. Proc Natl Acad Sci U S A 102 4459 4464
26. GuoXWilliamsJGSchugTTLiX 2010 DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1. J Biol Chem 285 13223 13232
27. KimMSPakYKJangPGNamkoongCChoiYS 2006 Role of hypothalamic Foxo1 in the regulation of food intake and energy homeostasis. Nat Neurosci 9 901 906
28. WuQZhangYXuJShenP 2005 Regulation of hunger-driven behaviors by neural ribosomal S6 kinase in Drosophila. Proc Natl Acad Sci U S A 102 13289 13294
29. IkeyaTGalicMBelawatPNairzKHafenE 2002 Nutrient-dependent expression of insulin-like peptides from neuroendocrine cells in the CNS contributes to growth regulation in Drosophila. Current Biology 12 1293 1300
30. HuangHTindallDJ 2007 Dynamic FoxO transcription factors. J Cell Sci 120 2479 2487
31. PuigOMattilaJ 2011 Understanding Forkhead box class O function: lessons from Drosophila melanogaster. Antioxid Redox Signal 14 635 647
32. BrunetABonniAZigmondMJLinMZJuoP 1999 Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96 857 868
33. NielsenMDLuoXBiteauBSyversonKJasperH 2008 14-3-3 Epsilon antagonizes FoxO to control growth, apoptosis and longevity in Drosophila. Aging Cell 7 688 699
34. MatsuzakiHDaitokuHHattaMAoyamaHYoshimochiK 2005 Acetylation of Foxo1 alters its DNA-binding ability and sensitivity to phosphorylation. Proc Natl Acad Sci U S A 102 11278 11283
35. ParkJSongWJChungKC 2009 Function and regulation of Dyrk1A: towards understanding Down syndrome. Cell Mol Life Sci 66 3235 3240
36. KorenbergJRChenXNSchipperRSunZGonskyR 1994 Down syndrome phenotypes: the consequences of chromosomal imbalance. Proc Natl Acad Sci U S A 91 4997 5001
37. MaggeSNO'NeillKLShultsJStallingsVAStettlerN 2008 Leptin levels among prepubertal children with Down syndrome compared with their siblings. J Pediatr 152 321 326
38. MelvilleCACooperSAMcGrotherCWThorpCFCollacottR 2005 Obesity in adults with Down syndrome: a case-control study. J Intellect Disabil Res 49 125 133
39. ObiciSFengZKarkaniasGBaskinDGRossettiL 2002 Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats. Nat Neurosci 5 566 572
40. SipolsAJBaskinDGSchwartzMW 1995 Effect of intracerebroventricular insulin infusion on diabetic hyperphagia and hypothalamic neuropeptide gene expression. Diabetes 44 147 151
41. VargheseJLimSFCohenSM 2010 Drosophila miR-14 regulates insulin production and metabolism through its target, sugarbabe. Genes Dev 24 2748 2753
42. RulifsonEJKimSKNusseR 2002 Ablation of insulin-producing neurons in flies: growth and diabetic phenotypes. Science 296 1118 1120
43. MinKJYamamotoRBuchSPankratzMTatarM 2008 Drosophila lifespan control by dietary restriction independent of insulin-like signaling. Aging Cell 7 199 206
44. GronkeSClarkeDFBroughtonSAndrewsTDPartridgeL 2010 Molecular evolution and functional characterization of Drosophila insulin-like peptides. PLoS Genet 6 e1000857 doi:10.1371/journal.pgen.1000857
45. McLeodCJWangLWongCJonesDL 2010 Stem cell dynamics in response to nutrient availability. Current Biology 20 2100 2105
46. RootCMKoKIJafariAWangJW 2011 Presynaptic facilitation by neuropeptide signaling mediates odor-driven food search. Cell 145 133 144
47. RubinGMSpradlingAC 1982 Genetic transformation of Drosophila with transposable element vectors. Science 218 348 353
48. GriswoldAJChangKTRunkoAPKnightMAMinKT 2008 Sir2 mediates apoptosis through JNK-dependent pathways in Drosophila. Proc Natl Acad Sci U S A 105 8673 8678
49. Iijima-AndoKWuPDrierEAIijimaKYinJC 2005 cAMP-response element-binding protein and heat-shock protein 70 additively suppress polyglutamine-mediated toxicity in Drosophila. Proc Natl Acad Sci U S A 102 10261 10266
50. OhlmeyerJTKalderonD 1997 Dual pathways for induction of wingless expression by protein kinase A and Hedgehog in Drosophila embryos. Genes Dev 11 2250 2258
51. UenoKKohatsuSClayCForteMIsonoK 2006 Gsalpha is involved in sugar perception in Drosophila melanogaster. J Neurosci 26 6143 6152
52. BrandAHPerrimonN 1993 Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118 401 415
53. XuKZhengXSehgalA 2008 Regulation of feeding and metabolism by neuronal and peripheral clocks in Drosophila. Cell Metab 8 289 300
54. WongRPiperMDBlancEPartridgeL 2008 Pitfalls of measuring feeding rate in the fruit fly Drosophila melanogaster. Nat Methods 5 214 215 author reply 215
55. AhnKJJeongHKChoiHSRyooSRKimYJ 2006 DYRK1A BAC transgenic mice show altered synaptic plasticity with learning and memory defects. Neurobiol Dis 22 463 472
56. TelemanAAHietakangasVSayadianACCohenSM 2008 Nutritional control of protein biosynthetic capacity by insulin via Myc in Drosophila. Cell Metab 7 21 32
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