Astakine 2—the Dark Knight Linking Melatonin to Circadian Regulation in Crustaceans


Daily, circadian rhythms influence essentially all living organisms and affect many physiological processes from sleep and nutrition to immunity. This ability to respond to environmental daily rhythms has been conserved along evolution, and it is found among species from bacteria to mammals. The hematopoietic process of the crayfish Pacifastacus leniusculus is under circadian control and is tightly regulated by astakines, a new family of cytokines sharing a prokineticin (PROK) domain. The expression of AST1 and AST2 are light-dependent, and this suggests an evolutionarily conserved function for PROK domain proteins in mediating circadian rhythms. Vertebrate PROKs are transmitters of circadian rhythms of the suprachiasmatic nucleus (SCN) in the brain of mammals, but the mechanism by which they function is unknown. Here we demonstrate that high AST2 expression is induced by melatonin in the brain. We identify RACK1 as a binding protein of AST2 and further provide evidence that a complex between AST2 and RACK1 functions as a negative-feedback regulator of the circadian clock. By DNA mobility shift assay, we showed that the AST2-RACK1 complex will interfere with the binding between BMAL1 and CLK and inhibit the E-box binding activity of the complex BMAL1-CLK. Finally, we demonstrate by gene knockdown that AST2 is necessary for melatonin-induced inhibition of the complex formation between BMAL1 and CLK during the dark period. In summary, we provide evidence that melatonin regulates AST2 expression and thereby affects the core clock of the crustacean brain. This process may be very important in all animals that have AST2 molecules, i.e. spiders, ticks, crustaceans, scorpions, several insect groups such as Hymenoptera, Hemiptera, and Blattodea, but not Diptera and Coleoptera. Our findings further reveal an ancient evolutionary role for the prokineticin superfamily protein that links melatonin to direct regulation of the core clock gene feedback loops.


Vyšlo v časopise: Astakine 2—the Dark Knight Linking Melatonin to Circadian Regulation in Crustaceans. PLoS Genet 9(3): e32767. doi:10.1371/journal.pgen.1003361
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1003361

Souhrn

Daily, circadian rhythms influence essentially all living organisms and affect many physiological processes from sleep and nutrition to immunity. This ability to respond to environmental daily rhythms has been conserved along evolution, and it is found among species from bacteria to mammals. The hematopoietic process of the crayfish Pacifastacus leniusculus is under circadian control and is tightly regulated by astakines, a new family of cytokines sharing a prokineticin (PROK) domain. The expression of AST1 and AST2 are light-dependent, and this suggests an evolutionarily conserved function for PROK domain proteins in mediating circadian rhythms. Vertebrate PROKs are transmitters of circadian rhythms of the suprachiasmatic nucleus (SCN) in the brain of mammals, but the mechanism by which they function is unknown. Here we demonstrate that high AST2 expression is induced by melatonin in the brain. We identify RACK1 as a binding protein of AST2 and further provide evidence that a complex between AST2 and RACK1 functions as a negative-feedback regulator of the circadian clock. By DNA mobility shift assay, we showed that the AST2-RACK1 complex will interfere with the binding between BMAL1 and CLK and inhibit the E-box binding activity of the complex BMAL1-CLK. Finally, we demonstrate by gene knockdown that AST2 is necessary for melatonin-induced inhibition of the complex formation between BMAL1 and CLK during the dark period. In summary, we provide evidence that melatonin regulates AST2 expression and thereby affects the core clock of the crustacean brain. This process may be very important in all animals that have AST2 molecules, i.e. spiders, ticks, crustaceans, scorpions, several insect groups such as Hymenoptera, Hemiptera, and Blattodea, but not Diptera and Coleoptera. Our findings further reveal an ancient evolutionary role for the prokineticin superfamily protein that links melatonin to direct regulation of the core clock gene feedback loops.


Zdroje

1. RosbashM, AlladaR, DembinskaM, GuoWQ, LeM, et al. (1996) A Drosophila circadian clock. Cold Spring Harb Symp Quant Biol 61: 265–278.

2. WeaverDR (1998) The suprachiasmatic nucleus: a 25-year retrospective. J Biol Rhythms 13: 100–112.

3. Helfrich-ForsterC, StenglM, HombergU (1998) Organization of the circadian system in insects. Chronobiol Int 15: 567–594.

4. StoneEF, FultonBO, AyresJS, PhamLN, ZiauddinJ, et al. (2012) The circadian clock protein timeless regulates phagocytosis of bacteria in Drosophila. PLoS Pathog 8: e1002445 doi:10.1371/journal.ppat.1002445

5. AlladaR, EmeryP, TakahashiJS, RosbashM (2001) Stopping time: the genetics of fly and mouse circadian clocks. Annu Rev Neurosci 24: 1091–1119.

6. LowreyPL, TakahashiJS (2004) Mammalian circadian biology: elucidating genome-wide levels of temporal organization. Annu Rev Genomics Hum Genet 5: 407–441.

7. WangGK, OusleyA, DarlingtonTK, ChenD, ChenY, et al. (2001) Regulation of the cycling of timeless (tim) RNA. J Neurobiol 47: 161–175.

8. KingDP, ZhaoY, SangoramAM, WilsbacherLD, TanakaM, et al. (1997) Positional cloning of the mouse circadian clock gene. Cell 89: 641–653.

9. RoblesMS, BoyaultC, KnuttiD, PadmanabhanK, WeitzCJ (2010) Identification of RACK1 and protein kinase Calpha as integral components of the mammalian circadian clock. Science 327: 463–466.

10. SaperCB, ScammellTE, LuJ (2005) Hypothalamic regulation of sleep and circadian rhythms. Nature 437: 1257–1263.

11. JohnsonRF, MooreRY, MorinLP (1988) Loss of entrainment and anatomical plasticity after lesions of the hamster retinohypothalamic tract. Brain Res 460: 297–313.

12. CassoneVM, ChesworthMJ, ArmstrongSM (1986) Entrainment of rat circadian rhythms by daily injection of melatonin depends upon the hypothalamic suprachiasmatic nuclei. Physiol Behav 36: 1111–1121.

13. MaestroniGJ, ContiA, PierpaoliW (1986) Role of the pineal gland in immunity. Circadian synthesis and release of melatonin modulates the antibody response and antagonizes the immunosuppressive effect of corticosterone. J Neuroimmunol 13: 19–30.

14. HardelandR, PoeggelerB (2003) Non-vertebrate melatonin. J Pineal Res 34: 233–241.

15. PoirelVJ, BoggioV, DardenteH, PevetP, Masson-PevetM, et al. (2003) Contrary to other non-photic cues, acute melatonin injection does not induce immediate changes of clock gene mRNA expression in the rat suprachiasmatic nuclei. Neuroscience 120: 745–755.

16. KrauchiK, Wirz-JusticeA (2001) Circadian clues to sleep onset mechanisms. Neuropsychopharmacology 25: S92–96.

17. SharmaVK, SingaravelM, SubbarajR, ChandrashekaranMK (1999) Timely administration of melatonin accelerates reentrainment to phase-shifted light-dark cycles in the field mouse Mus booduga. Chronobiol Int 16: 163–170.

18. ShibataS, CassoneVM, MooreRY (1989) Effects of melatonin on neuronal activity in the rat suprachiasmatic nucleus in vitro. Neurosci Lett 97: 140–144.

19. DijkDJ, CajochenC (1997) Melatonin and the circadian regulation of sleep initiation, consolidation, structure, and the sleep EEG. J Biol Rhythms 12: 627–635.

20. LissoniP, RovelliF, BrivioF, BrivioO, FumagalliL (1998) Circadian secretions of IL-2, IL-12, IL-6 and IL-10 in relation to the light/dark rhythm of the pineal hormone melatonin in healthy humans. Nat Immun 16: 1–5.

21. PetrovskyN (2001) Towards a unified model of neuroendocrine-immune interaction. Immunol Cell Biol 79: 350–357.

22. SandemanD, SandemanR, DerbyC, SchmidtM (1992) Morphology of the brain of crayfish, crabs and spiny lobsters: a common nomenclature for homologous structures. Biol Bull 183: 304–326.

23. SullivanJM, GencoMC, MarlowED, BentonJL, BeltzBS, et al. (2009) Brain photoreceptor pathways contributing to circadian rhythmicity in crayfish. Chronobiol Int 26: 1136–1168.

24. Escamilla-ChimalEG, Velazquez-AmadoRM, FiordelisioT, Fanjul-MolesML (2010) Putative pacemakers of crayfish show clock proteins interlocked with circadian oscillations. J Exp Biol 213: 3723–3733.

25. WithyachumnarnkulB, AjpruS, RachawongS, Pongsa-AsawapaiboonA, SumridthongA (1999) Sexual dimorphism in N-acetyltransferase and melatonin levels in the giant freshwater prawn Macrobrachium rosenbergii de Man. J Pineal Res 26: 174–177.

26. TildenAR, AltJ, BrummerK, GrothR, HerwigK, et al. (2001) Influence of photoperiod on N-acetyltransferase activity and melatonin in the fiddler crab Uca pugilator. Gen Comp Endocrinol 122: 233–237.

27. Mendoza-VargasL, Solis-ChagoyanH, Benitez-KingG, Fuentes-PardoB (2009) MT2-like melatonin receptor modulates amplitude receptor potential in visual cells of crayfish during a 24-hour cycle. Comp Biochem Physiol A Mol Integr Physiol 154: 486–492.

28. ChengMY, BullockCM, LiC, LeeAG, BermakJC, et al. (2002) Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus. Nature 417: 405–410.

29. PittendrighCS (1993) Temporal organization: reflections of a Darwinian clock-watcher. Annu Rev Physiol 55: 16–54.

30. WilsbacherLD, YamazakiS, HerzogED, SongEJ, RadcliffeLA, et al. (2002) Photic and circadian expression of luciferase in mPeriod1-luc transgenic mice invivo. Proc Natl Acad Sci U S A 99: 489–494.

31. LinX, NovotnyM, SöderhällK, SöderhällI (2010) Ancient cytokines, the role of astakines as hematopoietic growth factors. J Biol Chem 285: 28577–28586.

32. WatthanasurorotA, SöderhällK, JiravanichpaisalP, SöderhällI (2011) An ancient cytokine, astakine, mediates circadian regulation of invertebrate hematopoiesis. Cell Mol Life Sci 68: 315–323.

33. TildenAR, BrauchR, BallR, JanzeAM, GhaffariAH, et al. (2003) Modulatory effects of melatonin on behavior, hemolymph metabolites, and neurotransmitter release in crayfish. Brain Res 992: 252–262.

34. Ruiz CarrilloD, ChandrasekaranR, NilssonM, CornvikT, LiewCW, et al. (2012) Structure of human Rack1 protein at a resolution of 2.45 A. Acta Crystallogr Sect F Struct Biol Cryst Commun 68: 867–872.

35. Mendez-FerrerS, ChowA, MeradM, FrenettePS (2009) Circadian rhythms influence hematopoietic stem cells. Curr Opin Hematol 16: 235–242.

36. MonnierJ, SamsonM (2008) Cytokine properties of prokineticins. FEBS J 275: 4014–4021.

37. NegriL, LattanziR, GianniniE, CanestrelliM, NicotraA, et al. (2009) Bv8/Prokineticins and their Receptors A New Pronociceptive System. Int Rev Neurobiol 85: 145–157.

38. LinX, SöderhällI (2011) Crustacean hematopoiesis and the astakine cytokines. Blood 117: 6417–6424.

39. ProsserHM, BradleyA, CheshamJE, EblingFJ, HastingsMH, et al. (2007) Prokineticin receptor 2 (Prokr2) is essential for the regulation of circadian behavior by the suprachiasmatic nuclei. Proc Natl Acad Sci U S A 104: 648–653.

40. NegriL, LattanziR, GianniniE, ColucciMA, MignognaG, et al. (2005) Biological activities of Bv8 analogues. Br J Pharmacol 146: 625–632.

41. ChenJ, KueiC, SuttonS, WilsonS, YuJ, et al. (2005) Identification and pharmacological characterization of prokineticin 2 beta as a selective ligand for prokineticin receptor 1. Mol Pharmacol 67: 2070–2076.

42. UrayamaK, GuiliniC, MessaddeqN, HuK, SteenmanM, et al. (2007) The prokineticin receptor-1 (GPR73) promotes cardiomyocyte survival and angiogenesis. FASEB J 21: 2980–2993.

43. HardelandR, CardinaliDP, SrinivasanV, SpenceDW, BrownGM, et al. (2011) Melatonin–a pleiotropic, orchestrating regulator molecule. Prog Neurobiol 93: 350–384.

44. VerdeMA, Barriga-MontoyaC, Fuentes-PardoB (2007) Pigment dispersing hormone generates a circadian response to light in the crayfish, Procambarus clarkii. Comp Biochem Physiol A Mol Integr Physiol 147: 983–992.

45. ShearmanLP, SriramS, WeaverDR, MaywoodES, ChavesI, et al. (2000) Interacting molecular loops in the mammalian circadian clock. Science 288: 1013–1019.

46. OishiK, SakamotoK, OkadaT, NagaseT, IshidaN (1998) Antiphase circadian expression between BMAL1 and period homologue mRNA in the suprachiasmatic nucleus and peripheral tissues of rats. Biochem Biophys Res Commun 253: 199–203.

47. IshikawaT, HirayamaJ, KobayashiY, TodoT (2002) Zebrafish CRY represses transcription mediated by CLOCK-BMAL heterodimer without inhibiting its binding to DNA. Genes Cells 7: 1073–1086.

48. BaeK, LeeC, SidoteD, ChuangKY, EderyI (1998) Circadian regulation of a Drosophila homolog of the mammalian Clock gene: PER and TIM function as positive regulators. Mol Cell Biol 18: 6142–6151.

49. GlossopNR, LyonsLC, HardinPE (1999) Interlocked feedback loops within the Drosophila circadian oscillator. Science 286: 766–768.

50. GiebultowiczJM, StanewskyR, HallJC, HegeDM (2000) Transplanted Drosophila excretory tubules maintain circadian clock cycling out of phase with the host. Curr Biol 10: 107–110.

51. YamazakiS, NumanoR, AbeM, HidaA, TakahashiR, et al. (2000) Resetting central and peripheral circadian oscillators in transgenic rats. Science 288: 682–685.

52. LeeC, BaeK, EderyI (1998) The Drosophila CLOCK protein undergoes daily rhythms in abundance, phosphorylation, and interactions with the PER-TIM complex. Neuron 21: 857–867.

53. LeeC, BaeK, EderyI (1999) PER and TIM inhibit the DNA binding activity of a Drosophila CLOCK-CYC/dBMAL1 heterodimer without disrupting formation of the heterodimer: a basis for circadian transcription. Mol Cell Biol 19: 5316–5325.

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