and the BTB Adaptor Are Key Regulators of Sleep Homeostasis and a Dopamine Arousal Pathway in Drosophila

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Sleep is homeostatically regulated, such that sleep drive reflects the duration of prior wakefulness. However, despite the discovery of genes important for sleep, a coherent molecular model for sleep homeostasis has yet to emerge. To better understand the function and regulation of sleep, we employed a reverse-genetics approach in Drosophila. An insertion in the BTB domain protein CG32810/insomniac (inc) exhibited one of the strongest baseline sleep phenotypes thus far observed, a ∼10 h sleep reduction. Importantly, this is coupled to a reduced homeostatic response to sleep deprivation, consistent with a disrupted sleep homeostat. Knockdown of the INC-interacting protein, the E3 ubiquitin ligase Cul3, results in reduced sleep duration, consolidation, and homeostasis, suggesting an important role for protein turnover in mediating INC effects. Interestingly, inc and Cul3 expression in post-mitotic neurons during development contributes to their adult sleep functions. Similar to flies with increased dopaminergic signaling, loss of inc and Cul3 result in hyper-arousability to a mechanical stimulus in adult flies. Furthermore, the inc sleep duration phenotype can be rescued by pharmacological inhibition of tyrosine hydroxylase, the rate-limiting enzyme for dopamine biosynthesis. Taken together, these results establish inc and Cul3 as important new players in setting the sleep homeostat and a dopaminergic arousal pathway in Drosophila.

Vyšlo v časopise: and the BTB Adaptor Are Key Regulators of Sleep Homeostasis and a Dopamine Arousal Pathway in Drosophila. PLoS Genet 8(10): e32767. doi:10.1371/journal.pgen.1003003
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003003

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Zdroje

1. HendricksJC, FinnSM, PanckeriKA, ChavkinJ, WilliamsJA, et al. (2000) Rest in Drosophila is a sleep-like state. Neuron 25: 129–138.

2. ShawPJ, CirelliC, GreenspanRJ, TononiG (2000) Correlates of sleep and waking in Drosophila melanogaster. Science 287: 1834–1837.

3. CirelliC, LaVauteTM, TononiG (2005) Sleep and wakefulness modulate gene expression in Drosophila. J Neurochem 94: 1411–1419.

4. KohK, JoinerWJ, WuMN, YueZ, SmithCJ, et al. (2008) Identification of SLEEPLESS, a sleep-promoting factor. Science 321: 372–376.

5. WuMN, JoinerWJ, DeanT, YueZ, SmithCJ, et al. (2010) SLEEPLESS, a Ly-6/neurotoxin family member, regulates the levels, localization and activity of Shaker. Nat Neurosci 13: 69–75.

6. BusheyD, HuberR, TononiG, CirelliC (2007) Drosophila Hyperkinetic mutants have reduced sleep and impaired memory. J Neurosci 27: 5384–5393.

7. ShangY, HaynesP, PirezN, HarringtonKI, GuoF, et al. (2011) Imaging analysis of clock neurons reveals light buffers the wake-promoting effect of dopamine. Nat Neurosci 14: 889–895.

8. LebestkyT, ChangJS, DankertH, ZelnikL, KimYC, et al. (2009) Two different forms of arousal in Drosophila are oppositely regulated by the dopamine D1 receptor ortholog DopR via distinct neural circuits. Neuron 64: 522–536.

9. KumeK, KumeS, ParkSK, HirshJ, JacksonFR (2005) Dopamine is a regulator of arousal in the fruit fly. J Neurosci 25: 7377–7384.

10. AndreticR, van SwinderenB, GreenspanRJ (2005) Dopaminergic modulation of arousal in Drosophila. Curr Biol 15: 1165–1175.

11. FoltenyiK, GreenspanRJ, NewportJW (2007) Activation of EGFR and ERK by rhomboid signaling regulates the consolidation and maintenance of sleep in Drosophila. Nat Neurosci 10: 1160–1167.

12. HendricksJC, WilliamsJA, PanckeriK, KirkD, TelloM, et al. (2001) A non-circadian role for cAMP signaling and CREB activity in Drosophila rest homeostasis. Nat Neurosci 4: 1108–1115.

13. NakaiY, HoriuchiJ, TsudaM, TakeoS, AkahoriS, et al. (2011) Calcineurin and Its Regulator Sra/DSCR1 Are Essential for Sleep in Drosophila. J Neurosci 31: 12759–12766.

14. SeugnetL, SuzukiY, MerlinG, GottschalkL, DuntleySP, et al. (2011) Notch signaling modulates sleep homeostasis and learning after sleep deprivation in Drosophila. Curr Biol 21: 835–840.

15. CirelliC, BusheyD, HillS, HuberR, KreberR, et al. (2005) Reduced sleep in Drosophila Shaker mutants. Nature 434: 1087–1092.

16. BayonY, TrinidadAG, de la PuertaML, Del Carmen RodriguezM, BogetzJ, et al. (2008) KCTD5, a putative substrate adaptor for cullin3 ubiquitin ligases. Febs J 275: 3900–3910.

17. ZimmermanJE, RizzoW, ShockleyKR, RaizenDM, NaidooN, et al. (2006) Multiple mechanisms limit the duration of wakefulness in Drosophila brain. Physiol Genomics 27: 337–350.

18. KeeganKP, PradhanS, WangJP, AlladaR (2007) Meta-analysis of Drosophila circadian microarray studies identifies a novel set of rhythmically expressed genes. PLoS Comput Biol 3: e208 doi:10.1371/journal.pcbi.0030208.

19. KadenerS, StoleruD, McDonaldM, NawatheanP, RosbashM (2007) Clockwork Orange is a transcriptional repressor and a new Drosophila circadian pacemaker component. Genes Dev 21: 1675–1686.

20. RyderE, BlowsF, AshburnerM, Bautista-LlacerR, CoulsonD, et al. (2004) The DrosDel collection: a set of P-element insertions for generating custom chromosomal aberrations in Drosophila melanogaster. Genetics 167: 797–813.

21. StavropoulosN, YoungM (2011) insomniac and Cullin-3 Regulate Sleep and Wakefulness in Drosophila. Neuron 72: 964–1040.

22. DietzlG, ChenD, SchnorrerF, SuKC, BarinovaY, et al. (2007) A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila. Nature 448: 151–156.

23. JoinerWJ, CrockerA, WhiteBH, SehgalA (2006) Sleep in Drosophila is regulated by adult mushroom bodies. Nature 441: 757–760.

24. PitmanJL, McGillJJ, KeeganKP, AlladaR (2006) A dynamic role for the mushroom bodies in promoting sleep in Drosophila. Nature 441: 753–756.

25. CrockerA, ShahidullahM, LevitanIB, SehgalA (2010) Identification of a neural circuit that underlies the effects of octopamine on sleep:wake behavior. Neuron 65: 670–681.

26. DonleaJM, ThimganMS, SuzukiY, GottschalkL, ShawPJ (2011) Inducing sleep by remote control facilitates memory consolidation in Drosophila. Science 332: 1571–1576.

27. DementievaIS, TereshkoV, McCrossanZA, SolomahaE, ArakiD, et al. (2009) Pentameric assembly of potassium channel tetramerization domain-containing protein 5. J Mol Biol 387: 175–191.

28. OsterwalderT, YoonKS, WhiteBH, KeshishianH (2001) A conditional tissue-specific transgene expression system using inducible GAL4. Proc Natl Acad Sci U S A 98: 12596–12601.

29. ZhuS, PerezR, PanM, LeeT (2005) Requirement of Cul3 for axonal arborization and dendritic elaboration in Drosophila mushroom body neurons. J Neurosci 25: 4189–4197.

30. TomitaJ, MitsuyoshiM, UenoT, AsoY, TanimotoH, et al. (2011) Pan-neuronal knockdown of calcineurin reduces sleep in the fruit fly, Drosophila melanogaster. The Journal of neuroscience : the official journal of the Society for Neuroscience 31: 13137–13183.

31. DzirasaK, RibeiroS, CostaR, SantosLM, LinSC, et al. (2006) Dopaminergic control of sleep-wake states. J Neurosci 26: 10577–10589.

32. LalouxC, DerambureP, HoudayerE, JacquessonJM, BordetR, et al. (2008) Effect of dopaminergic substances on sleep/wakefulness in saline- and MPTP-treated mice. J Sleep Res 17: 101–110.

33. AgostoJ, ChoiJC, PariskyKM, StilwellG, RosbashM, et al. (2008) Modulation of GABA(A) receptor desensitization uncouples sleep onset and maintenance in Drosophila. Nat Neurosci 11: 354–359.

34. ChungBY, KilmanVL, KeathJR, PitmanJL, AlladaR (2009) The GABA(A) receptor RDL acts in peptidergic PDF neurons to promote sleep in Drosophila. Curr Biol 19: 386–390.

35. PariskyKM, AgostoJ, PulverSR, ShangY, KuklinE, et al. (2008) PDF cells are a GABA-responsive wake-promoting component of the Drosophila sleep circuit. Neuron 60: 672–682.

36. NeckameyerWS (1998) Dopamine and mushroom bodies in Drosophila: experience-dependent and -independent aspects of sexual behavior. Learning and Memory 5: 157–165.

37. BangS, HyunS, HongS-T, KangJ, JeongK, et al. (2011) Dopamine signalling in mushroom bodies regulates temperature-preference behaviour in Drosophila. PLoS Genet 7: e1001346 doi:10.1371/journal.pgen.1001346.

38. SwarupS, HarbisonS, HahnL, MorozovaT, YamamotoA, et al. (2012) Extensive epistasis for olfactory behaviour, sleep and waking activity in Drosophila melanogaster. Genetics research 94: 9–29.

39. SarinS, BertrandV, BigelowH, BoyanovA, DoitsidouM, et al. (2010) Analysis of multiple ethyl methanesulfonate-mutagenized Caenorhabditis elegans strains by whole-genome sequencing. Genetics 185: 417–447.

40. DjagaevaI, DoronkinS (2009) COP9 limits dendritic branching via Cullin3-dependent degradation of the actin-crosslinking BTB-domain protein Kelch. PLoS ONE 4: e7598 doi:10.1371/journal.pone.0007598.

41. VolkowND, WangGJ, TelangF, FowlerJS, LoganJ, et al. (2008) Sleep deprivation decreases binding of [11C]raclopride to dopamine D2/D3 receptors in the human brain. J Neurosci 28: 8454–8461.

42. TandbergE, LarsenJP, KarlsenK (1999) Excessive daytime sleepiness and sleep benefit in Parkinson's disease: a community-based study. Mov Disord 14: 922–927.

43. OndoWG, Dat VuongK, KhanH, AtassiF, KwakC, et al. (2001) Daytime sleepiness and other sleep disorders in Parkinson's disease. Neurology 57: 1392–1396.

44. ClarenbachP (2000) Parkinson's disease and sleep. J Neurol 247 Suppl 4: IV/20–23.

45. ArnulfI, KonofalE, Merino-AndreuM, HouetoJL, MesnageV, et al. (2002) Parkinson's disease and sleepiness: an integral part of PD. Neurology 58: 1019–1024.

46. RiemenspergerT, IsabelG, CoulomH, NeuserK, SeugnetL, et al. (2011) Behavioral consequences of dopamine deficiency in the Drosophila central nervous system. Proc Natl Acad Sci U S A 108: 834–839.

47. CattersonJH, Knowles-BarleyS, JamesK, HeckMM, HarmarAJ, et al. (2010) Dietary modulation of Drosophila sleep-wake behaviour. PLoS ONE 5: e12062 doi:10.1371/journal.pone.0012062.

48. AndreticR, van SwinderenB, GreenspanR (2005) Dopaminergic modulation of arousal in Drosophila. Current biology : CB 15: 1165–1240.

49. AndreticR, KimYC, JonesFS, HanKA, GreenspanRJ (2008) Drosophila D1 dopamine receptor mediates caffeine-induced arousal. Proc Natl Acad Sci U S A 105: 20392–20397.

50. ShangY, HaynesP, PírezN, HarringtonK, GuoF, et al. (2011) Imaging analysis of clock neurons reveals light buffers the wake-promoting effect of dopamine. Nature Neuroscience 14: 889–984.

51. SeugnetL, SuzukiY, VineL, GottschalkL, ShawPJ (2008) D1 receptor activation in the mushroom bodies rescues sleep-loss-induced learning impairments in Drosophila. Curr Biol 18: 1110–1117.

52. BusheyD, TononiG, CirelliC (2011) Sleep and synaptic homeostasis: structural evidence in Drosophila. Science 332: 1576–1581.

53. GilestroGF, TononiG, CirelliC (2009) Widespread changes in synaptic markers as a function of sleep and wakefulness in Drosophila. Science 324: 109–112.

54. DonleaJM, RamananN, ShawPJ (2009) Use-dependent plasticity in clock neurons regulates sleep need in Drosophila. Science 324: 105–108.

55. FreemanA, PranskiE, MillerR, RadmardS, BernhardD, et al. (2012) Sleep fragmentation and motor restlessness in a Drosophila model of restless legs syndrome. Current biology : CB 22: 1142–1150.

56. AlladaR, KadenerS, NandakumarN, RosbashM (2003) A recessive mutant of Drosophila Clock reveals a role in circadian rhythm amplitude. Embo J 22: 3367–3375.

57. ChenJ, CondronBG (2008) Branch architecture of the fly larval abdominal serotonergic neurons. Dev Biol 320: 30–38.

58. LinHH, LaiJS, ChinAL, ChenYC, ChiangAS (2007) A map of olfactory representation in the Drosophila mushroom body. Cell 128: 1205–1217.

59. RulifsonEJ, KimSK, NusseR (2002) Ablation of insulin-producing neurons in flies: growth and diabetic phenotypes. Science 296: 1118–1120.

60. NgM, RoordaRD, LimaSQ, ZemelmanBV, MorcilloP, et al. (2002) Transmission of olfactory information between three populations of neurons in the antennal lobe of the fly. Neuron 36: 463–474.

61. KobayashiM, MichautL, InoA, HonjoK, NakajimaT, et al. (2006) Differential microarray analysis of Drosophila mushroom body transcripts using chemical ablation. Proc Natl Acad Sci U S A 103: 14417–14422.

62. PfeiffenbergerC, LearBC, KeeganKP, AlladaR (2010) Processing sleep data created with the Drosophila Activity Monitoring (DAM) System. Cold Spring Harb Protoc 2010: pdb prot5520.

63. NeckameyerWS, WoodromeS, HoltB, MayerA (2000) Dopamine and senescence in Drosophila melanogaster. Neurobiol Aging 21: 145–152.