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The cGMP-Dependent Protein Kinase EGL-4 Regulates Nociceptive Behavioral Sensitivity


Signaling levels within sensory neurons must be tightly regulated to allow cells to integrate information from multiple signaling inputs and to respond to new stimuli. Herein we report a new role for the cGMP-dependent protein kinase EGL-4 in the negative regulation of G protein-coupled nociceptive chemosensory signaling. C. elegans lacking EGL-4 function are hypersensitive in their behavioral response to low concentrations of the bitter tastant quinine and exhibit an elevated calcium flux in the ASH sensory neurons in response to quinine. We provide the first direct evidence for cGMP/PKG function in ASH and propose that ODR-1, GCY-27, GCY-33 and GCY-34 act in a non-cell-autonomous manner to provide cGMP for EGL-4 function in ASH. Our data suggest that activated EGL-4 dampens quinine sensitivity via phosphorylation and activation of the regulator of G protein signaling (RGS) proteins RGS-2 and RGS-3, which in turn downregulate Gα signaling and behavioral sensitivity.


Vyšlo v časopise: The cGMP-Dependent Protein Kinase EGL-4 Regulates Nociceptive Behavioral Sensitivity. PLoS Genet 9(7): e32767. doi:10.1371/journal.pgen.1003619
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003619

Souhrn

Signaling levels within sensory neurons must be tightly regulated to allow cells to integrate information from multiple signaling inputs and to respond to new stimuli. Herein we report a new role for the cGMP-dependent protein kinase EGL-4 in the negative regulation of G protein-coupled nociceptive chemosensory signaling. C. elegans lacking EGL-4 function are hypersensitive in their behavioral response to low concentrations of the bitter tastant quinine and exhibit an elevated calcium flux in the ASH sensory neurons in response to quinine. We provide the first direct evidence for cGMP/PKG function in ASH and propose that ODR-1, GCY-27, GCY-33 and GCY-34 act in a non-cell-autonomous manner to provide cGMP for EGL-4 function in ASH. Our data suggest that activated EGL-4 dampens quinine sensitivity via phosphorylation and activation of the regulator of G protein signaling (RGS) proteins RGS-2 and RGS-3, which in turn downregulate Gα signaling and behavioral sensitivity.


Zdroje

1. BargmannCI, ThomasJH, HorvitzHR (1990) Chemosensory cell function in the behavior and development of Caenorhabditis elegans. Cold Spring Harb Symp Quant Biol 55: 529–538.

2. KaplanJM, HorvitzHR (1993) A dual mechanosensory and chemosensory neuron in Caenorhabditis elegans. Proc Natl Acad Sci U S A 90: 2227–2231.

3. HartAC, KassJ, ShapiroJE, KaplanJM (1999) Distinct signaling pathways mediate touch and osmosensory responses in a polymodal sensory neuron. J Neurosci 19: 1952–1958.

4. SambongiY, NagaeT, LiuY, YoshimizuT, TakedaK, et al. (1999) Sensing of cadmium and copper ions by externally exposed ADL, ASE, and ASH neurons elicits avoidance response in Caenorhabditis elegans. Neuroreport 10: 753–757.

5. TroemelER (1999) Chemosensory signaling in C. elegans. Bioessays 21: 1011–1020.

6. HilliardMA, BargmannCI, BazzicalupoP (2002) C. elegans responds to chemical repellents by integrating sensory inputs from the head and the tail. Curr Biol 12: 730–734.

7. HilliardMA, BergamascoC, ArbucciS, PlasterkRH, BazzicalupoP (2004) Worms taste bitter: ASH neurons, QUI-1, GPA-3 and ODR-3 mediate quinine avoidance in Caenorhabditis elegans. EMBO J 23: 1101–1111.

8. HilliardMA, ApicellaAJ, KerrR, SuzukiH, BazzicalupoP, et al. (2005) In vivo imaging of C. elegans ASH neurons: cellular response and adaptation to chemical repellents. EMBO J 24: 63–72.

9. ChatzigeorgiouM, BangS, HwangSW, SchaferWR (2013) tmc-1 encodes a sodium-sensitive channel required for salt chemosensation in C. elegans. Nature 494: 95–99.

10. ChandrashekarJ, HoonMA, RybaNJ, ZukerCS (2006) The receptors and cells for mammalian taste. Nature 444: 288–294.

11. PalmerRK (2007) The pharmacology and signaling of bitter, sweet, and umami taste sensing. Mol Interv 7: 87–98.

12. DryerL, BerghardA (1999) Odorant receptors: a plethora of G-protein-coupled receptors. Trends Pharmacol Sci 20: 413–417.

13. McCuddenCR, HainsMD, KimpleRJ, SiderovskiDP, WillardFS (2005) G-protein signaling: back to the future. Cell Mol Life Sci 62: 551–577.

14. Bargmann CI (2006) Chemosensation in C. elegans. In: Community TCeR, editor. WormBook: WormBook.

15. AokiR, YagamiT, SasakuraH, OguraK, KajiharaY, et al. (2011) A seven-transmembrane receptor that mediates avoidance response to dihydrocaffeic acid, a water-soluble repellent in Caenorhabditis elegans. J Neurosci 31: 16603–16610.

16. RoayaieK, CrumpJG, SagastiA, BargmannCI (1998) The Gα protein ODR-3 mediates olfactory and nociceptive function and controls cilium morphogenesis in C. elegans olfactory neurons. Neuron 20: 55–67.

17. EspositoG, AmorosoMR, BergamascoC, Di SchiaviE, BazzicalupoP (2010) The G protein regulators EGL-10 and EAT-16, the Giα GOA-1 and the Gqα EGL-30 modulate the response of the C. elegans ASH polymodal nociceptive sensory neurons to repellents. BMC Biol 8: 138.

18. JansenG, ThijssenKL, WernerP, van der HorstM, HazendonkE, et al. (1999) The complete family of genes encoding G proteins of Caenorhabditis elegans. Nat Genet 21: 414–419.

19. RossEM, WilkieTM (2000) GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins. Annu Rev Biochem 69: 795–827.

20. HollingerS, HeplerJR (2002) Cellular regulation of RGS proteins: modulators and integrators of G protein signaling. Pharmacol Rev 54: 527–559.

21. ChenCK, BurnsME, HeW, WenselTG, BaylorDA, et al. (2000) Slowed recovery of rod photoresponse in mice lacking the GTPase accelerating protein RGS9-1. Nature 403: 557–560.

22. KrispelCM, ChenD, MellingN, ChenYJ, MartemyanovKA, et al. (2006) RGS expression rate-limits recovery of rod photoresponses. Neuron 51: 409–416.

23. von BuchholtzL, ElischerA, TareilusE, GoukaR, KaiserC, et al. (2004) RGS21 is a novel regulator of G protein signalling selectively expressed in subpopulations of taste bud cells. European Journal of Neuroscience 19: 1535–1544.

24. MclaughlinSK, MckinnonPJ, MargolskeeRF (1992) Gustducin is a taste-cell-specific G-protein closely related to the transducins. Nature 357: 563–569.

25. MingD, Ruiz-AvilaL, MargolskeeRF (1998) Charcterization and solubilization of bitter-responsive receptors that couple to gustducin. Proc Natl Acad Sci U S A 95: 8933–8938.

26. WongGT, GannonKS, MargolskeeRF (1996) Transduction of bitter and sweet taste by gustducin. Nature 381: 796–800.

27. HuangL, ShankerYG, DubauskaiteJ, ZhengJZ, YanW, et al. (1999) Gγ13 colocalized with gustducin in taste receptor cells and mediates IP3 responses to bitter denatonium. Nat Neurosci 2: 1055–1062.

28. FerkeyDM, HydeR, HaspelG, DionneHM, HessHA, et al. (2007) C. elegans G protein regulator RGS-3 controls sensitivity to sensory stimuli. Neuron 53: 39–52.

29. HofmannF (2005) The biology of cyclic GMP-dependent protein kinases. J Biol Chem 280: 1–4.

30. LincolnTM, DeyN, SellakH (2001) Invited review: cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the regulation of tone to gene expression. J Appl Physiol 91: 1421–1430.

31. KoeppenM, FeilR, SieglD, FeilS, HofmannF, et al. (2004) cGMP-dependent protein kinase mediates NO- but not acetylcholine-induced dilations in resistance vessels in vivo. Hypertension 44: 952–955.

32. PfeiferA, KlattP, MassbergS, NyL, SausbierM, et al. (1998) Defective smooth muscle regulation in cGMP kinase I-deficient mice. EMBO J 17: 3045–3051.

33. SausbierM, SchubertR, VoigtV, HirneissC, PfeiferA, et al. (2000) Mechanisms of NO/cGMP-dependent vasorelaxation. Circ Res 87: 825–830.

34. MassbergS, SausbierM, KlattP, BauerM, PfeiferA, et al. (1999) Increased adhesion and aggregation of platelets lacking cyclic guanosine 3′,5′-monophosphate kinase I. J Exp Med 189: 1255–1264.

35. FrancisSH, BuschJL, CorbinJD, SibleyD (2010) cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action. Pharmacol Rev 62: 525–563.

36. SchmidtH, WernerM, HeppenstallPA, HenningM, MoréMI, et al. (2002) cGMP-mediated signaling via cGKIα is required for the guidance and connectivity of sensory axons. J Cell Biol 159: 489–498.

37. TegederI, Del TurcoD, SchmidtkoA, SausbierM, FeilR, et al. (2004) Reduced inflammatory hyperalgesia with preservation of acute thermal nociception in mice lacking cGMP-dependent protein kinase I. Proc Natl Acad Sci U S A 101: 3253–3257.

38. WernerC, RaivichG, CowenM, StrekalovaT, SillaberI, et al. (2004) Importance of NO/cGMP signalling via cGMP-dependent protein kinase II for controlling emotionality and neurobehavioural effects of alcohol. Eur J Neurosci 20: 3498–3506.

39. Osei-OwusuP, SunX, DrenanRM, SteinbergTH, BlumerKJ (2007) Regulation of RGS2 and second messenger signaling in vascular smooth muscle cells by cGMP-dependent protein kinase. J Biol Chem 282: 31656–31665.

40. TangKM, WangGR, LuP, KarasRH, AronovitzM, et al. (2003) Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure. Nat Med 9: 1506–1512.

41. PedramA, RazandiM, KehrlJ, LevinER (2000) Natriuretic peptides inhibit G protein activation. Mediation through cross-talk betwen cyclic cGMP-dependent protein kinase and regulators of G protein-signaling proteins. Journal of Biological Chemistry 275: 8.

42. HuangJ, ZhouH, SM, SriwaiW, MurthyKS (2006) Inhibition of Gαq-dependent PLC-β activity by PKG and PKA is mediated by phosphorylation of RGS4 and GRK2. American Journal of Physiology Cell Physiology 292: 9.

43. Hu PJ (2007) Dauer. In: Community TCeR, editor. WormBook: WormBook.

44. Savage-Dunn C (2005) TGF-β signaling. In: Community TCeR, editor. WormBook: WormBook.

45. RaizenDM, CullisonKM, PackAI, SundaramMV (2006) A novel gain-of-function mutant of the cyclic GMP-dependent protein kinase egl-4 affects multiple physiological processes in Caenorhabditis elegans. Genetics 173: 177–187.

46. StansberryJ, BaudeEJ, TaylorMK, ChenPJ, JinSW, et al. (2001) A cGMP-dependent protein kinase is implicated in wild-type motility in C. elegans. Journal of Neurochemistry 76: 1177–1187.

47. DanielsSA, AilionM, ThomasJH, SenguptaP (2000) egl-4 acts through a transforming growth factor-β/SMAD pathway in Caenorhabditis elegans to regulate multiple neuronal circuits in response to sensory cues. Genetics 156: 123–141.

48. L'EtoileND, CoburnCM, EasthamJ, KistlerA, GallegosG, et al. (2002) The cyclic GMP-dependent protein kinase EGL-4 regulates olfactory adaptation in C. elegans. Neuron 36: 1079–1089.

49. LeeJI, O'HalloranDM, Eastham-AndersonJ, JuangBT, KayeJA, et al. (2010) Nuclear entry of a cGMP-dependent kinase converts transient into long-lasting olfactory adaptation. Proc Natl Acad Sci U S A 107: 6016–6021.

50. van der LindenAM, NolanKM, SenguptaP (2007) KIN-29 SIK regulates chemoreceptor gene expression via an MEF2 transcription factor and a class II HDAC. EMBO J 26: 358–370.

51. van der LindenAM, WienerS, YouYJ, KimK, AveryL, et al. (2008) The EGL-4 PKG acts with KIN-29 salt-inducible kinase and protein kinase A to regulate chemoreceptor gene expression and sensory behaviors in Caenorhabditis elegans. Genetics 180: 1475–1491.

52. LanjuinA, SenguptaP (2002) Regulation of chemosensory receptor expression and sensory signaling by the KIN-29 Ser/Thr kinase. Neuron 33: 369–381.

53. KuoJF (1974) Guanosine 3′:5′-monophosphate-dependent protein kinases in mammalian tissues. Proc Natl Acad Sci U S A 71: 4037–4041.

54. GillGN, HoldyKE, WaltonGM, KansteinCB (1976) Purification and characterization of 3′:5′-cyclic GMP-dependent protein kinase. Proc Natl Acad Sci U S A 73: 3918–3922.

55. GudiT, LohmannSM, PilzRB (1997) Regulation of gene expression by cyclic GMP-dependent protein kinase requires nuclear translocation of the kinase: identification of a nuclear localization signal. Mol Cell Biol 17: 5244–5254.

56. FrancisSH, CorbinJD (1994) Structure and function of cyclic nucleotide-dependent protein kinases. Annu Rev Physiol 56: 237–272.

57. O'HalloranDM, HamiltonOS, LeeJI, GallegosM, L'EtoileND (2012) Changes in cGMP levels affect the localization of EGL-4 in AWC in Caenorhabditis elegans. PLoS One 7: e31614.

58. HaoY, XuN, BoxAC, SchaeferL, KannanK, et al. (2011) Nuclear cGMP-dependent kinase regulates gene expression via activity-dependent recruitment of a conserved histone deacetylase complex. PLoS Genet 7: e1002065.

59. OrtizCO, EtchbergerJF, PosySL, Frokjaer-JensenC, LockeryS, et al. (2006) Searching for neuronal left/right asymmetry: genomewide analysis of nematode receptor-type guanylyl cyclases. Genetics 173: 131–149.

60. HiroseT, NakanoY, NagamatsuY, MisumiT, OhtaH, et al. (2003) Cyclic GMP-dependent protein kinase EGL-4 controls body size and lifespan in C. elegans. Development 130: 1089–1099.

61. TroemelER, ChouJH, DwyerND, ColbertHA, BargmannCI (1995) Divergent seven transmembrane receptors are candidate chemosensory receptors in C. elegans. Cell 83: 207–218.

62. KimK, SatoK, ShibuyaM, ZeigerDM, ButcherRA, et al. (2009) Two chemoreceptors mediate developmental effects of dauer pheromone in C. elegans. Science 326: 994–998.

63. EspositoG, Di SchiaviE, BergamascoC, BazzicalupoP (2007) Efficient and cell specific knock-down of gene function in targeted C. elegans neurons. Gene 395: 170–176.

64. ChaoMY, KomatsuH, FukutoHS, DionneHM, HartAC (2004) Feeding status and serotonin rapidly and reversibly modulate a Caenorhabditis elegans chemosensory circuit. Proc Natl Acad Sci U S A 101: 15512–15517.

65. FukutoHS, FerkeyDM, ApicellaAJ, LansH, SharmeenT, et al. (2004) G protein-coupled receptor kinase function is essential for chemosensation in C. elegans. Neuron 42: 581–593.

66. O'HalloranDM, Altshuler-KeylinS, LeeJI, L'EtoileND (2009) Regulators of AWC-mediated olfactory plasticity in Caenorhabditis elegans. PLoS Genet 5: e1000761.

67. NakaiJ, OhkuraM, ImotoK (2001) A high signal-to-noise Ca2+ probe composed of a single green fluorescent protein. Nat Biotechnol 19: 137–141.

68. MiyawakiA, LlopisJ, HeimR, McCafferyJM, AdamsJA, et al. (1997) Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin. Nature 388: 882–887.

69. TianL, HiresSA, MaoT, HuberD, ChiappeME, et al. (2009) Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators. Nat Methods 6: 875–881.

70. McGrathPT, XuY, AilionM, GarrisonJL, ButcherRA, et al. (2011) Parallel evolution of domesticated Caenorhabditis species targets pheromone receptor genes. Nature 477: 321–325.

71. HessHA, RoperJC, GrillSW, KoelleMR (2004) RGS-7 completes a receptor-independent heterotrimeric G protein cycle to asymmetrically regulate mitotic spindle positioning in C. elegans. Cell 119: 209–218.

72. DongMQ, ChaseD, PatikoglouGA, KoelleMR (2000) Multiple RGS proteins alter neural G protein signaling to allow C. elegans to rapidly change behavior when fed. Genes Dev 14: 2003–2014.

73. KennellyPJ, KrebsEG (1991) Consensus sequences as substrate specificity determinants for protein kinases and protein phosphatases. J Biol Chem 266: 15555–15558.

74. AitkenA, BilhamT, CohenP, AswadD, GreengardP (1981) A specific substrate from rabbit cerebellum for guanosine-3′:5′-monophosphate-dependent protein kinase. III. Amino acid sequences at the two phosphorylation sites. J Biol Chem 256: 3501–3506.

75. ThomasMK, FrancisSH, CorbinJD (1990) Substrate- and kinase-directed regulation of phosphorylation of a cGMP-binding phosphodiesterase by cGMP. J Biol Chem 265: 14971–14978.

76. EdlundB, ZetterqvistO, RagnarssonU, EngströmL (1977) Phosphorylation of synthetic peptides by (32P)ATP and cyclic GMP-stimulated protein kinase. Biochem Biophys Res Commun 79: 139–144.

77. BlomN, Sicheritz-PontenT, GuptaR, GammeltoftS, BrunakS (2004) Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence. Proteomics 4: 1633–1649.

78. HofmannF, FeilR, KleppischT, SchlossmannJ (2006) Function of cGMP-dependent protein kinases as revealed by gene deletion. Physiol Rev 86: 1–23.

79. BurnsME, ArshavskyVY (2005) Beyond counting photons: trials and trends in vertebrate visual transduction. Neuron 48: 387–401.

80. SohJW, MaoY, LiuL, ThompsonWJ, PamukcuR, et al. (2001) Protein kinase G activates the JNK1 pathway via phosphorylation of MEKK1. J Biol Chem 276: 16406–16410.

81. JohlfsMG, FiscusRR (2010) Protein kinase G type-Iα phosphorylates the apoptosis-regulating protein Bad at serine 155 and protects against apoptosis in N1E-115 cells. Neurochemistry International 56: 546–553.

82. SinghK, ChaoMY, SomersGA, KomatsuH, CorkinsME, et al. (2011) C. elegans Notch signaling regulates adult chemosensory response and larval molting quiescence. Curr Biol 21: 825–834.

83. NeherE, SakabaT (2008) Multiple roles of calcium ions in the regulation of neurotransmitter release. Neuron 59: 861–872.

84. KomalavilasP, LincolnTM (1994) Phosphorylation of the inositol 1,4,5-trisphosphate receptor by cyclic GMP-dependent protein kinase. J Biol Chem 269: 8701–8707.

85. WagnerLE2nd, LiWH, YuleDI (2003) Phosphorylation of type-1 inositol 1,4,5-trisphosphate receptors by cyclic nucleotide-dependent protein kinases: a mutational analysis of the functionally important sites in the S2+ and S2- splice variants. J Biol Chem 278: 45811–45817.

86. LuoC, GangadharanV, BaliKK, XieRG, AgarwalN, et al. (2012) Presynaptically localized cyclic GMP-dependent protein kinase 1 is a key determinant of spinal synaptic potentiation and pain hypersensitivity. PloS Biology 10: e1001283.

87. IkedaH, StarkJ, FischerH, WagnerM, DrdlaR, et al. (2006) Synaptic amplifier of inflammatory pain in the spinal dorsal horn. Science 312: 1659–1662.

88. KolhekarR, MellerST, GebhartGF (1993) Characterization of the role of spinal N-methyl-D-aspartate receptors in thermal nociception in the rat. Neuroscience 57: 385–395.

89. TrentC, TsuingN, HorvitzHR (1983) Egg-laying defective mutants of the nematode Caenorhabditis elegans. Genetics 104: 619–647.

90. ChaseDL, PatikoglouGA, KoelleMR (2001) Two RGS proteins that inhibit Gαo and Gαq signaling in C. elegans neurons require a Gβ5-like subunit for function. Curr Biol 11: 222–231.

91. RobatzekM, NiacarisT, StegerK, AveryL, ThomasJH (2001) eat-11 encodes GPB-2, a Gβ5 ortholog that interacts with Goα and Gqα to regulate C. elegans behavior. Curr Biol 11: 288–293.

92. van der LindenAM, SimmerF, CuppenE, PlasterkRH (2001) The G-protein β-subunit GPB-2 in Caenorhabditis elegans regulates the Goα-Gqα signaling network through interactions with the regulator of G-protein signaling proteins EGL-10 and EAT-16. Genetics 158: 221–235.

93. Chase DL, Koelle MR (2007) Biogenic amine neurotransmitters in C. elegans. In: Community TCeR, editor. WormBook: WormBook.

94. WraggRT, HapiakV, MillerSB, HarrisGP, GrayJ, et al. (2007) Tyramine and octopamine independently inhibit serotonin-stimulated aversive behaviors in Caenorhabditis elegans through two novel amine receptors. J Neurosci 27: 13402–13412.

95. HarrisGP, HapiakVM, WraggRT, MillerSB, HughesLJ, et al. (2009) Three distinct amine receptors operating at different levels within the locomotory circuit are each essential for the serotonergic modulation of chemosensation in Caenorhabditis elegans. J Neurosci 29: 1446–1456.

96. EzcurraM, TanizawaY, SwobodaP, SchaferWR (2011) Food sensitizes C. elegans avoidance behaviours through acute dopamine signalling. EMBO J 30: 1110–1122.

97. PotterLR (2011) Guanylyl cyclase structure, function and regulation. Cell Signal 23: 1921–1926.

98. LincolnTM, WuX, SellakH, DeyN, ChoiCS (2006) Regulation of vascular smooth muscle cell phenotype by cyclic GMP and cyclic GMP-dependent protein kinase. Front Biosci 11: 356–367.

99. HofmannF, BernhardD, LukowskiR, WeinmeisterP (2009) cGMP regulated protein kinases (cGK). Handb Exp Pharmacol 137–162.

100. ArshavskyVY, BurnsME (2012) Photoreceptor signaling: supporting vision across a wide range of light intensities. J Biol Chem 287: 1620–1626.

101. GarbersDL, ChrismanTD, WiegnP, KatafuchiT, AlbanesiJP, et al. (2006) Membrane guanylyl cyclase receptors: an update. Trends Endocrinol Metab 17: 251–258.

102. BrennerS (1974) The genetics of Caenorhabditis elegans. Genetics 77: 71–94.

103. MelloCC, KramerJM, StinchcombD, AmbrosV (1991) Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences. Embo J 10: 3959–3970.

104. FukushigeT, HawkinsMG, McGheeJD (1998) The GATA-factor elt-2 is essential for formation of the Caenorhabditis elegans intestine. Dev Biol 198: 286–302.

105. RongoC, WhitfieldCW, RodalA, KimSK, KaplanJM (1998) LIN-10 is a shared component of the polarized protein localization pathways in neurons and epithelia. Cell 94: 751–759.

106. EzakMJ, HongE, Chaparro-GarciaA, FerkeyDM (2010) Caenorhabditis elegans TRPV channels function in a modality-specific pathway to regulate response to aberrant sensory signaling. Genetics 185: 233–244.

107. ZimmerM, GrayJM, PokalaN, ChangAJ, KarowDS, et al. (2009) Neurons detect increases and decreases in oxygen levels using distinct guanylate cyclases. Neuron 61: 865–879.

108. L'EtoileND, BargmannCI (2000) Olfaction and odor discrimination are mediated by the C. elegans guanylyl cyclase ODR-1. Neuron 25: 575–586.

109. ChalasaniSH, KatoS, AlbrechtDR, NakagawaT, AbbottLF, et al. (2010) Neuropeptide feedback modifies odor-evoked dynamics in Caenorhabditis elegans olfactory neurons. Nat Neurosci 13: 615–621.

110. ChronisN, ZimmerM, BargmannCI (2007) Microfluidics for in vivo imaging of neuronal and behavioral activity in Caenorhabditis elegans. Nat Methods 4: 727–731.

111. EdelsteinA, AmodajN, HooverK, ValeR, StuurmanN (2010) Computer control of microscopes using µManager. Curr Protoc Mol Biol Chapter 14: Unit 14.20.

112. Wood WB (1988) The Nematode Caenorhabditis elegans; researchers TcoCe, editor. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory.

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