#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Nitric oxide mediates neuro-glial interaction that shapes Drosophila circadian behavior


Autoři: Anatoly Kozlov aff001;  Rafael Koch aff001;  Emi Nagoshi aff001
Působiště autorů: Department of Genetics and Evolution, Sciences III, University of Geneva, Quai Ernest-Ansermet, Switzerland aff001
Vyšlo v časopise: Nitric oxide mediates neuro-glial interaction that shapes Drosophila circadian behavior. PLoS Genet 16(6): e32767. doi:10.1371/journal.pgen.1008312
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008312

Souhrn

Drosophila circadian behavior relies on the network of heterogeneous groups of clock neurons. Short- and long-range signaling within the pacemaker circuit coordinates molecular and neural rhythms of clock neurons to generate coherent behavioral output. The neurochemistry of circadian behavior is complex and remains incompletely understood. Here we demonstrate that the gaseous messenger nitric oxide (NO) is a signaling molecule linking circadian pacemaker to rhythmic locomotor activity. We show that mutants lacking nitric oxide synthase (NOS) have behavioral arrhythmia in constant darkness, although molecular clocks in the main pacemaker neurons are unaffected. Behavioral phenotypes of mutants are due in part to the malformation of neurites of the main pacemaker neurons, s-LNvs. Using cell-type selective and stage-specific gain- and loss-of-function of NOS, we also demonstrate that NO secreted from diverse cellular clusters affect behavioral rhythms. Furthermore, we identify the perineurial glia, one of the two glial subtypes that form the blood-brain barrier, as the major source of NO that regulates circadian locomotor output. These results reveal for the first time the critical role of NO signaling in the Drosophila circadian system and highlight the importance of neuro-glial interaction in the neural circuit output.

Klíčová slova:

Biological locomotion – Circadian rhythms – Drosophila melanogaster – Chronobiology – Neurons – Nitric oxide – Pacemakers – RNA interference


Zdroje

1. Konopka RJ, Benzer S. Clock mutants of Drosophila melanogaster. Proc Natl Acad Sci U S A. 1971;68(9):2112–6. doi: 10.1073/pnas.68.9.2112 5002428

2. Hardin PE. Molecular genetic analysis of circadian timekeeping in Drosophila. Adv Genet. 2011;74:141–73. doi: 10.1016/B978-0-12-387690-4.00005-2 21924977

3. Hurley JM, Loros JJ, Dunlap JC. Circadian Oscillators: Around the Transcription-Translation Feedback Loop and on to Output. Trends Biochem Sci. 2016;41(10):834–46. doi: 10.1016/j.tibs.2016.07.009 27498225

4. Helfrich-Forster C, Yoshii T, Wulbeck C, Grieshaber E, Rieger D, Bachleitner W, et al. The lateral and dorsal neurons of Drosophila melanogaster: new insights about their morphology and function. Cold Spring Harb Symp Quant Biol. 2007;72:517–25. Epub 2008/04/19. doi: 10.1101/sqb.2007.72.063 18419311

5. Schubert FK, Hagedorn N, Yoshii T, Helfrich-Forster C, Rieger D. Neuroanatomical details of the lateral neurons of Drosophila melanogaster support their functional role in the circadian system. J Comp Neurol. 2018;526(7):1209–31. doi: 10.1002/cne.24406 29424420

6. Beckwith EJ, Ceriani MF. Communication between circadian clusters: The key to a plastic network. Febs Letters. 2015;589(22):3336–42. doi: 10.1016/j.febslet.2015.08.017 26297822

7. Frenkel L, Muraro NI, Beltran Gonzalez AN, Marcora MS, Bernabo G, Hermann-Luibl C, et al. Organization of Circadian Behavior Relies on Glycinergic Transmission. Cell Rep. 2017;19(1):72–85. doi: 10.1016/j.celrep.2017.03.034 28380364

8. Grima B, Chelot E, Xia R, Rouyer F. Morning and evening peaks of activity rely on different clock neurons of the Drosophila brain. Nature. 2004;431(7010):869–73. doi: 10.1038/nature02935 15483616

9. Kozlov A, Nagoshi E. Decoding Drosophila circadian pacemaker circuit. Curr Opin Insect Sci. 2019;36:33–8. doi: 10.1016/j.cois.2019.06.010 31376574

10. Picot M, Cusumano P, Klarsfeld A, Ueda R, Rouyer F. Light activates output from evening neurons and inhibits output from morning neurons in the Drosophila circadian clock. PLoS Biol. 2007;5(11):e315. doi: 10.1371/journal.pbio.0050315 18044989

11. Stoleru D, Peng Y, Agosto J, Rosbash M. Coupled oscillators control morning and evening locomotor behaviour of Drosophila. Nature. 2004;431(7010):862–8. Epub 2004/10/16. nature02926 [pii] doi: 10.1038/nature02926 15483615

12. Top D, Harms E, Syed S, Adams EL, Saez L. GSK-3 and CK2 Kinases Converge on Timeless to Regulate the Master Clock. Cell Rep. 2016;16(2):357–67. doi: 10.1016/j.celrep.2016.06.005 27346344

13. Abruzzi KC, Zadina A, Luo W, Wiyanto E, Rahman R, Guo F, et al. RNA-seq analysis of Drosophila clock and non-clock neurons reveals neuron-specific cycling and novel candidate neuropeptides. Plos Genet. 2017;13(2):e1006613. doi: 10.1371/journal.pgen.1006613 28182648

14. Beuchle D, Jaumouille E, Nagoshi E. The nuclear receptor unfulfilled is required for free-running clocks in Drosophila pacemaker neurons. Curr Biol. 2012;22(13):1221–7. doi: 10.1016/j.cub.2012.04.052 22658597

15. Jaumouille E, Machado Almeida P, Stahli P, Koch R, Nagoshi E. Transcriptional regulation via nuclear receptor crosstalk required for the Drosophila circadian clock. Curr Biol. 2015;25(11):1502–8. doi: 10.1016/j.cub.2015.04.017 26004759

16. King-Jones K, Thummel CS. Nuclear receptors—a perspective from Drosophila. Nat Rev Genet. 2005;6(4):311–23. doi: 10.1038/nrg1581 15803199

17. Alyagor I, Berkun V, Keren-Shaul H, Marmor-Kollet N, David E, Mayseless O, et al. Combining Developmental and Perturbation-Seq Uncovers Transcriptional Modules Orchestrating Neuronal Remodeling. Dev Cell. 2018;47(1):38–52 e6. doi: 10.1016/j.devcel.2018.09.013 30300589

18. Uryu O, Ameku T, Niwa R. Recent progress in understanding the role of ecdysteroids in adult insects: Germline development and circadian clock in the fruit fly Drosophila melanogaster. Zoological Lett. 2015;1:32. doi: 10.1186/s40851-015-0031-2 26605077

19. Caceres L, Necakov AS, Schwartz C, Kimber S, Roberts IJ, Krause HM. Nitric oxide coordinates metabolism, growth, and development via the nuclear receptor E75. Genes Dev. 2011;25(14):1476–85. doi: 10.1101/gad.2064111 21715559

20. Johnston DM, Sedkov Y, Petruk S, Riley KM, Fujioka M, Jaynes JB, et al. Ecdysone- and NO-mediated gene regulation by competing EcR/Usp and E75A nuclear receptors during Drosophila development. Mol Cell. 2011;44(1):51–61. doi: 10.1016/j.molcel.2011.07.033 21981918

21. Rabinovich D, Yaniv SP, Alyagor I, Schuldiner O. Nitric Oxide as a Switching Mechanism between Axon Degeneration and Regrowth during Developmental Remodeling. Cell. 2016;164(1–2):170–82. doi: 10.1016/j.cell.2015.11.047 26771490

22. Bicker G. Sources and targets of nitric oxide signalling in insect nervous systems. Cell Tissue Res. 2001;303(2):137–46. doi: 10.1007/s004410000321 11291761

23. Forstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012;33(7):829–37, 37a-37d. doi: 10.1093/eurheartj/ehr304 21890489

24. Lancaster JR Jr. A tutorial on the diffusibility and reactivity of free nitric oxide. Nitric Oxide. 1997;1(1):18–30. doi: 10.1006/niox.1996.0112 9701041

25. Toledo JC Jr., Augusto O. Connecting the chemical and biological properties of nitric oxide. Chem Res Toxicol. 2012;25(5):975–89. doi: 10.1021/tx300042g 22449080

26. Ding JM, Chen D, Weber ET, Faiman LE, Rea MA, Gillette MU. Resetting the biological clock: mediation of nocturnal circadian shifts by glutamate and NO. Science. 1994;266(5191):1713–7. doi: 10.1126/science.7527589 7527589

27. Melo L, Golombek DA, Ralph MR. Regulation of circadian photic responses by nitric oxide. J Biol Rhythms. 1997;12(4):319–26. doi: 10.1177/074873049701200404 9438880

28. Watanabe A, Ono M, Shibata S, Watanabe S. Effect of a nitric oxide synthase inhibitor, N-nitro-L-arginine methylester, on light-induced phase delay of circadian rhythm of wheel-running activity in golden hamsters. Neurosci Lett. 1995;192(1):25–8. doi: 10.1016/0304-3940(95)11599-r 7675302

29. Golombek DA, Agostino PV, Plano SA, Ferreyra GA. Signaling in the mammalian circadian clock: the NO/cGMP pathway. Neurochem Int. 2004;45(6):929–36. doi: 10.1016/j.neuint.2004.03.023 15312987

30. Plano SA, Agostino PV, de la Iglesia HO, Golombek DA. cGMP-phosphodiesterase inhibition enhances photic responses and synchronization of the biological circadian clock in rodents. PLoS One. 2012;7(5):e37121. doi: 10.1371/journal.pone.0037121 22590651

31. Weber ET, Gannon RL, Rea MA. cGMP-dependent protein kinase inhibitor blocks light-induced phase advances of circadian rhythms in vivo. Neurosci Lett. 1995;197(3):227–30. doi: 10.1016/0304-3940(95)11961-u 8552305

32. Muller U. The nitric oxide system in insects. Prog Neurobiol. 1997;51(3):363–81. doi: 10.1016/s0301-0082(96)00067-6 9089793

33. Zhou L, Zhu DY. Neuronal nitric oxide synthase: structure, subcellular localization, regulation, and clinical implications. Nitric Oxide. 2009;20(4):223–30. doi: 10.1016/j.niox.2009.03.001 19298861

34. Stasiv Y, Regulski M, Kuzin B, Tully T, Enikolopov G. The Drosophila nitric-oxide synthase gene (dNOS) encodes a family of proteins that can modulate NOS activity by acting as dominant negative regulators. J Biol Chem. 2001;276(45):42241–51. doi: 10.1074/jbc.M105066200 11526108

35. Stasiv Y, Kuzin B, Regulski M, Tully T, Enikolopov G. Regulation of multimers via truncated isoforms: a novel mechanism to control nitric-oxide signaling. Genes Dev. 2004;18(15):1812–23. doi: 10.1101/gad.298004 15256486

36. Kojima H, Hirotani M, Nakatsubo N, Kikuchi K, Urano Y, Higuchi T, et al. Bioimaging of nitric oxide with fluorescent indicators based on the rhodamine chromophore. Anal Chem. 2001;73(9):1967–73. doi: 10.1021/ac001136i 11354477

37. Yakubovich N, Silva EA, O'Farrell PH. Nitric oxide synthase is not essential for Drosophila development. Curr Biol. 2010;20(4):R141–2. doi: 10.1016/j.cub.2009.12.011 20178753

38. Gibbs SM, Becker A, Hardy RW, Truman JW. Soluble guanylate cyclase is required during development for visual system function in Drosophila. J Neurosci. 2001;21(19):7705–14. doi: 10.1523/JNEUROSCI.21-19-07705.2001 11567060

39. Gibbs SM, Truman JW. Nitric oxide and cyclic GMP regulate retinal patterning in the optic lobe of Drosophila. Neuron. 1998;20(1):83–93. doi: 10.1016/s0896-6273(00)80436-5 9459444

40. Kozlov A, Jaumouille E, Machado Almeida P, Koch R, Rodriguez J, Abruzzi KC, et al. A Screening of UNF Targets Identifies Rnb, a Novel Regulator of Drosophila Circadian Rhythms. J Neurosci. 2017;37(28):6673–85. doi: 10.1523/JNEUROSCI.3286-16.2017 28592698

41. Kuntz S, Poeck B, Strauss R. Visual Working Memory Requires Permissive and Instructive NO/cGMP Signaling at Presynapses in the Drosophila Central Brain. Curr Biol. 2017;27(5):613–23. doi: 10.1016/j.cub.2016.12.056 28216314

42. Colasanti M, Venturini G. Nitric oxide in invertebrates. Mol Neurobiol. 1998;17(1–3):157–74. doi: 10.1007/BF02802029 9887451

43. Muller U, Buchner E. Histochemical localization of NADPH-diaphorase in the adult Drosophila brain. Is nitric oxide a neuronal messenger also in insects? Naturwissenschaften. 1993;80(11):524–6. doi: 10.1007/BF01140811 8264807

44. Shah S, Hyde DR. Two Drosophila genes that encode the alph and beta subunits of the brain soluble guanylyl cyclase. J Biol Chem. 1995;270(25):15368–76. doi: 10.1074/jbc.270.25.15368 7797526

45. Kremer MC, Jung C, Batelli S, Rubin GM, Gaul U. The glia of the adult Drosophila nervous system. Glia. 2017;65(4):606–38. doi: 10.1002/glia.23115 28133822

46. Kula-Eversole E, Nagoshi E, Shang YH, Rodriguez J, Allada R, Rosbash M. Surprising gene expression patterns within and between PDF-containing circadian neurons in Drosophila. P Natl Acad Sci USA. 2010;107(30):13497–502. doi: 10.1073/pnas.1002081107 20624977

47. Nagoshi E, Sugino K, Kula E, Okazaki E, Tachibana T, Nelson S, et al. Dissecting differential gene expression within the circadian neuronal circuit of Drosophila. Nat Neurosci. 2010;13(1):60–8. Epub 2009/12/08. nn.2451 [pii] doi: 10.1038/nn.2451 19966839

48. Sims DW, Humphries NE, Hu N, Medan V, Berni J. Optimal searching behaviour generated intrinsically by the central pattern generator for locomotion. Elife. 2019;8. doi: 10.7554/eLife.50316 31674911

49. McGuire SE, Mao Z, Davis RL. Spatiotemporal gene expression targeting with the TARGET and gene-switch systems in Drosophila. Sci STKE. 2004;2004(220):pl6. doi: 10.1126/stke.2202004pl6 14970377

50. DeSalvo MK, Hindle SJ, Rusan ZM, Orng S, Eddison M, Halliwill K, et al. The Drosophila surface glia transcriptome: evolutionary conserved blood-brain barrier processes. Front Neurosci. 2014;8:346. doi: 10.3389/fnins.2014.00346 25426014

51. Hindle SJ, Bainton RJ. Barrier mechanisms in the Drosophila blood-brain barrier. Front Neurosci. 2014;8:414. doi: 10.3389/fnins.2014.00414 25565944

52. Zhang SL, Yue Z, Arnold DM, Artiushin G, Sehgal A. A Circadian Clock in the Blood-Brain Barrier Regulates Xenobiotic Efflux. Cell. 2018;173(1):130–9 e10. doi: 10.1016/j.cell.2018.02.017 29526461

53. Enikolopov G, Banerji J, Kuzin B. Nitric oxide and Drosophila development. Cell Death Differ. 1999;6(10):956–63. doi: 10.1038/sj.cdd.4400577 10556972

54. Aso Y, Ray RP, Long X, Bushey D, Cichewicz K, Ngo TT, et al. Nitric oxide acts as a cotransmitter in a subset of dopaminergic neurons to diversify memory dynamics. Elife. 2019;8. doi: 10.7554/eLife.49257 31724947

55. Foster JD, Dunford C, Sillar KT, Miles GB. Nitric oxide-mediated modulation of the murine locomotor network. J Neurophysiol. 2014;111(3):659–74. doi: 10.1152/jn.00378.2013 24259545

56. Kyriakatos A, Molinari M, Mahmood R, Grillner S, Sillar KT, El Manira A. Nitric oxide potentiation of locomotor activity in the spinal cord of the lamprey. J Neurosci. 2009;29(42):13283–91. doi: 10.1523/JNEUROSCI.3069-09.2009 19846716

57. McLean DL, Sillar KT. Nitric oxide selectively tunes inhibitory synapses to modulate vertebrate locomotion. J Neurosci. 2002;22(10):4175–84. doi: 20026377 12019335

58. Herrero A, Duhart JM, Ceriani MF. Neuronal and Glial Clocks Underlying Structural Remodeling of Pacemaker Neurons in Drosophila. Front Physiol. 2017;8:918. doi: 10.3389/fphys.2017.00918 29184510

59. Ng FS, Tangredi MM, Jackson FR. Glial cells physiologically modulate clock neurons and circadian behavior in a calcium-dependent manner. Curr Biol. 2011;21(8):625–34. doi: 10.1016/j.cub.2011.03.027 21497088

60. Suh J, Jackson FR. Drosophila ebony activity is required in glia for the circadian regulation of locomotor activity. Neuron. 2007;55(3):435–47. doi: 10.1016/j.neuron.2007.06.038 17678856

61. Pardee KI, Xu X, Reinking J, Schuetz A, Dong A, Liu S, et al. The structural basis of gas-responsive transcription by the human nuclear hormone receptor REV-ERBbeta. PLoS Biol. 2009;7(2):e43. doi: 10.1371/journal.pbio.1000043 19243223

62. Pirez N, Bernabei-Cornejo SG, Fernandez-Acosta M, Duhart JM, Ceriani MF. Contribution of non-circadian neurons to the temporal organization of locomotor activity. Biol Open. 2019;8(1). doi: 10.1242/bio.039628 30530810

63. Jenett A, Rubin GM, Ngo TT, Shepherd D, Murphy C, Dionne H, et al. A GAL4-driver line resource for Drosophila neurobiology. Cell Rep. 2012;2(4):991–1001. doi: 10.1016/j.celrep.2012.09.011 23063364

64. Gummadova JO, Coutts GA, Glossop NR. Analysis of the Drosophila Clock promoter reveals heterogeneity in expression between subgroups of central oscillator cells and identifies a novel enhancer region. J Biol Rhythms. 2009;24(5):353–67. doi: 10.1177/0748730409343890 19755581

65. Renn SC, Park JH, Rosbash M, Hall JC, Taghert PH. A pdf neuropeptide gene mutation and ablation of PDF neurons each cause severe abnormalities of behavioral circadian rhythms in Drosophila. Cell. 1999;99(7):791–802. doi: 10.1016/s0092-8674(00)81676-1 10619432

66. Sepp KJ, Schulte J, Auld VJ. Peripheral glia direct axon guidance across the CNS/PNS transition zone. Dev Biol. 2001;238(1):47–63. doi: 10.1006/dbio.2001.0411 11783993

67. Connolly JB, Roberts IJ, Armstrong JD, Kaiser K, Forte M, Tully T, et al. Associative learning disrupted by impaired Gs signaling in Drosophila mushroom bodies. Science. 1996;274(5295):2104–7. doi: 10.1126/science.274.5295.2104 8953046

68. Aso Y, Grubel K, Busch S, Friedrich AB, Siwanowicz I, Tanimoto H. The Mushroom Body of Adult Drosophila Characterized by GAL4 Drivers. Journal of Neurogenetics. 2009;23(1–2):156–U29. Pii 907683862 doi: 10.1080/01677060802471718 19140035

69. Yamada T, Okabe M, Hiromi Y. EDL/MAE regulates EGF-mediated induction by antagonizing Ets transcription factor Pointed. Development. 2003;130(17):4085–96. doi: 10.1242/dev.00624 12874129

70. Luo L, Liao YJ, Jan LY, Jan YN. Distinct morphogenetic functions of similar small GTPases: Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion. Genes Dev. 1994;8(15):1787–802. doi: 10.1101/gad.8.15.1787 7958857

71. Helfrich-Forster C, Shafer OT, Wulbeck C, Grieshaber E, Rieger D, Taghert P. Development and morphology of the clock-gene-expressing lateral neurons of Drosophila melanogaster. J Comp Neurol. 2007;500(1):47–70. Epub 2006/11/14. doi: 10.1002/cne.21146 17099895

72. Blanchardon E, Grima B, Klarsfeld A, Chelot E, Hardin PE, Preat T, et al. Defining the role of Drosophila lateral neurons in the control of circadian rhythms in motor activity and eclosion by targeted genetic ablation and PERIOD protein overexpression. Eur J Neurosci. 2001;13(5):871–88. doi: 10.1046/j.0953-816x.2000.01450.x 11264660

73. Sabado V, Vienne L, Nunes JM, Rosbash M, Nagoshi E. Fluorescence circadian imaging reveals a PDF-dependent transcriptional regulation of the Drosophila molecular clock. Sci Rep. 2017;7:41560. doi: 10.1038/srep41560 28134281

74. Kuppers-Munther B, Letzkus JJ, Luer K, Technau G, Schmidt H, Prokop A. A new culturing strategy optimises Drosophila primary cell cultures for structural and functional analyses. Dev Biol. 2004;269(2):459–78. doi: 10.1016/j.ydbio.2004.01.038 15110713


Článek vyšel v časopise

PLOS Genetics


2020 Číslo 6
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Důležitost adherence při depresivním onemocnění
nový kurz
Autoři: MUDr. Eliška Bartečková, Ph.D.

Koncepce osteologické péče pro gynekology a praktické lékaře
Autoři: MUDr. František Šenk

Sekvenční léčba schizofrenie
Autoři: MUDr. Jana Hořínková, Ph.D.

Hypertenze a hypercholesterolémie – synergický efekt léčby
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Multidisciplinární zkušenosti u pacientů s diabetem
Autoři: Prof. MUDr. Martin Haluzík, DrSc., prof. MUDr. Vojtěch Melenovský, CSc., prof. MUDr. Vladimír Tesař, DrSc.

Všechny kurzy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#