Neuropeptide Gene Families in Caenorhabditis elegans

  • Chris LiEmail author
  • Kyuhyung Kim
Part of the Advances in Experimental Medicine and Biology book series (volume 692)


Neuropeptides are short sequences of amino acids that function in all multicellular organisms to communicate information between cells. The first sequence of a neuropeptide was reported in 19701 and the number of identified neuropeptides remained relatively small until the 1990s when the DNA sequence of multiple genomes revealed treasure troves of information. By blasting away at the genome, gene families, the sizes of which were previously unknown, could now be determined. This information has led to an exponential increase in the number of putative neuropeptides and their respective gene families.

The molecular biology age greatly benefited the neuropeptide field in the nematode Caenorhabditis elegans. Its genome was among the first to be sequenced2 and this allowed us the opportunity to screen the genome for neuropeptide genes. Initially, the screening was slow, as the Genefinder and BLAST programs had difficulty identifying small genes and peptides. However, as the bioinformatics programs improved, the extent of the neuropeptide gene families in C. elegans gradually emerged.


Caenorhabditis Elegans Nematode Caenorhabditis Elegans Ventral Cord Pharyngeal Neuron Head Neuron 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Chang MM, Leeman SE. Isolation of a sialogogic peptide from bovine hypothalamic tissue and its characterization as substance P. J Biol Chem 1970; 245:4784–4790.PubMedGoogle Scholar
  2. 2.
    Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 1998; 282:2012–2018.Google Scholar
  3. 3.
    Duret L, Guex N, Peitsch MC et al. New insulin-like proteins with atypical disulfide bond pattern characterized in Caenorhabditis elegans by comparative sequence analysis and homology modeling. Genome Research 1998; 8:348–353.PubMedGoogle Scholar
  4. 4.
    Gregoire FM, Chomiki N, Kachinskas D et al. Cloning and developmental regulation of a novel member of the insulin-like gene family in Caenorhabditis elegans. Biochem Biophys Res Commun 1998; 249:385–390.PubMedGoogle Scholar
  5. 5.
    Kawano T, Ito Y, Ishiguro M et al. Molecular cloning and characterization of a new insulin/IGF-like peptide of the nematode Caenorhabditis elegans. Biochem Biophys Res Commun 2000; 273:431–436.PubMedGoogle Scholar
  6. 6.
    Li W, Kennedy SG, Ruvkun G. daf-28 encodes a C. elegans insulin superfamily member that is regulated by environmental cues and acts in the DAF-2 signaling pathway. Gene Dev 2003; 17:844–858.PubMedGoogle Scholar
  7. 7.
    Pierce SB, Costa M, Wisotzkey R et al. Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family. Genes Dev 2001; 15:672–686.PubMedGoogle Scholar
  8. 8.
    Price DA, Greenberg MJ. Structure of a molluscan cardioexcitatory neuropeptide. Science 1977; 197:670–671.PubMedGoogle Scholar
  9. 9.
    Dockray GJ. The expanding family of-RFamide peptides and their effects on feeding behaviour. Exp Physiol 2004; 89:229–235.PubMedGoogle Scholar
  10. 10.
    Li C. The ever-expanding neuropeptide gene families in the nematode Caenorhabditis elegans. Parasitology 131 Suppl, 2005; S109–127.PubMedGoogle Scholar
  11. 11.
    Li C, Kim K, Nelson LS. FMRFamide-related neuropeptide gene family in Caenorhabditis elegans. Brain Res 1999; 848:26–34.PubMedGoogle Scholar
  12. 12.
    Nelson LS, Kim K, Memmott JE et al. FMRFamide-related gene family in the nematode, Caenorhabditis elegans. Brain Res Mol Brain Res 1998; 58:103–111.PubMedGoogle Scholar
  13. 13.
    Li C, Nelson LS, Kim K et al. Neuropeptide gene families in the nematode Caenorhabditis elegans. Ann N Y Acad Sci 1999; 897:239–252.PubMedGoogle Scholar
  14. 14.
    Nathoo AN, Moeller RA, Westlund BA et al. Identification of neuropeptide-like protein gene families in Caenorhabditis elegans and other species. Proc Natl Acad Sci USA 2001; 98:14000–14005.PubMedGoogle Scholar
  15. 15.
    Blumenthal T. Trans-splicing and polycistronic transcription in Caenorhabditis elegans. Trends Genet 1995; 11:132–136.PubMedGoogle Scholar
  16. 16.
    Kim K, Li C. Expression and regulation of an FMRFamide-related neuropeptide gene family in Caenorhabditis elegans. J Comp Neurol 2004; 475:540–550.PubMedGoogle Scholar
  17. 17.
    McVeigh P, Leech S, Mair GR et al. Analysis of FMRFamide-like peptide (FLP) diversity in phylum Nematoda. Int J Parasitol 2005; 35:1043–1060.PubMedGoogle Scholar
  18. 18.
    Rosoff ML, Burglin TR, Li C. Alternatively spliced transcripts of the flp-1 gene encode distinct FMRFamide-like peptides in Caenorhabditis elegans. J Neurosci 1992; 12:2356–2361.PubMedGoogle Scholar
  19. 19.
    Couillault C, Pujol N, Reboul J et al. TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM. Nature Immunology 2004; 5:488–494.PubMedGoogle Scholar
  20. 20.
    Kim K. Function of a FMRFamide-related neuropeptide gene family in Caenorhabditis elegans. PhD thesis, Boston, MA: Boston University 2003.Google Scholar
  21. 21.
    Sithigorngul P, Stretton AO, Cowden C. A versatile dot-ELISA method with femtomole sensitivity for detecting small peptides. J Immunol Methods 1991; 141:23–32.PubMedGoogle Scholar
  22. 22.
    Strand FL. Neuropeptides 1999. (Cambridge, MA: MIT Press).Google Scholar
  23. 23.
    Sossin WS, Sweet-Cordero A, Scheller RH. Dale’s hypothesis revisited: different neuropeptides derived from a common prohormone are targeted to different processes. Proc Natl Acad Sci USA 1990; 87:4845–4848.PubMedGoogle Scholar
  24. 24.
    Scamuffa N, Calvo F, Chretien M et al. Proprotein convertases: lessons from knockouts. FASEB J 2006; 20:1954–1963.PubMedGoogle Scholar
  25. 25.
    Steiner DF. The proprotein convertases. Curr Opin Chem Biol 1998; 2:31–39.PubMedGoogle Scholar
  26. 26.
    Lindberg I, Tu B, Muller L. Cloning and functional analysis of C. elegans 7B2. DNA Cell Biol 1998; 17:727–734.PubMedGoogle Scholar
  27. 27.
    Sieburth D, Ch’ng Q, Dybbs M et al. Systematic analysis of genes required for synapse structure and function. Nature 2005; 436:510–517.PubMedGoogle Scholar
  28. 28.
    Husson SJ, Clynen E, Baggerman G et al. Discovering neuropeptides in Caenorhabditis elegans by two dimensional liquid chromatography and mass spectrometry. Biochem Biophys Res Commun 2005; 335:76–86.PubMedGoogle Scholar
  29. 29.
    Marks NJ, Maule AG, Geary TG et al. APEASPFIRFamide, a novel FMRFamide-related decapeptide from Caenorhabditis elegans: structure and myoactivity. Biochem Biophys Res Commun 1997; 231:591–595.PubMedGoogle Scholar
  30. 30.
    Marks NJ, Maule AG, Geary TG et al. KSAYMRFamide (PF3/AF8) is present in the free-living nematode, Caenorhabditis elegans. Biochem Biophys Res Commun 1998; 248:422–425.PubMedGoogle Scholar
  31. 31.
    Marks NJ, Maule AG, Li C et al. Isolation, pharmacology and gene organization of KPSFVRFamide: a neuropeptide from Caenorhabditis elegans. Biochem Biophys Res Commun 1999; 254:222–230.PubMedGoogle Scholar
  32. 32.
    Marks NJ, Shaw C, Halton DW et al. Isolation and preliminary biological assessment of AADGAPLIRFamide and SVPGVLRFamide from Caenorhabditis elegans. Biochem Biophys Res Commun 2001; 286:1170–1176.PubMedGoogle Scholar
  33. 33.
    Marks NJ, Shaw C, Maule AG et al. Isolation of AF2 (KHEYLRFamide) from Caenorhabditis elegans: evidence for the presence of more than one FMRFamide-related peptide-encoding gene. Biochem Biophys Res Commun 1995; 217:845–851.PubMedGoogle Scholar
  34. 34.
    Marder E, Calabrese RL, Nusbaum MP et al. Distribution and partial characterization of FMRFamide-like peptides in the stomatogastric nervous systems of the rock crab, Cancer borealis and the spiny lobster, Panulirus interruptus. J Comp Neurol 1987; 259:150–163.PubMedGoogle Scholar
  35. 35.
    Kass J, Jacob TC, Kim P et al. The EGL-3 proprotein convertase regulates mechanosensory responses of Caenorhabditis elegans. J Neurosci 2001; 21:9265–9272.PubMedGoogle Scholar
  36. 36.
    Husson SJ, Clynen E, Baggerman G et al. Defective processing of neuropeptide precursors in Caenorhabditis elegans lacking proprotein convertase 2 (KPC-2/EGL-3): mutant analysis by mass spectrometry. J Neurochem 2006; 98:1999–2012.PubMedGoogle Scholar
  37. 37.
    Trent C, Tsuing N, Horvitz HR. Egg-laying defective mutants of the nematode Caenorhabditis elegans. Genetics 1983; 104:619–647.PubMedGoogle Scholar
  38. 38.
    Thacker C, Rose AM. A look at the Caenorhabditis elegans Kex2/Subtilisin-like proprotein convertase family. Bioessays 2000; 22:545–553.PubMedGoogle Scholar
  39. 39.
    Kimura KD, Tissenbaum HA, Liu Y et al. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 1997; 277:942–946.PubMedGoogle Scholar
  40. 40.
    Thacker C, Peters K, Srayko M et al. The bli-4 locus of Caenorhabditis elegans encodes structurally distinct kex2/subtilisin-like endoproteases essential for early development and adult morphology. Genes Dev 1995; 9:956–971.PubMedGoogle Scholar
  41. 41.
    Thomas JH. Genetic analysis of defecation in Caenorhabditis elegans. Genetics 1990; 124:855–872.PubMedGoogle Scholar
  42. 42.
    Reiner DJ, Thomas JH. Reversal of a muscle response to GABA during C. elegans male development. J Neurosci 1995; 15:6094–6102.PubMedGoogle Scholar
  43. 43.
    Miller DM 3rd, Ortiz I, Berliner GC et al. Differential localization of two myosins within nematode thick filaments. Cell 1983; 34:477–490.PubMedGoogle Scholar
  44. 44.
    MacLeod AR, Waterston RH, Fishpool RM et al. Identification of the structural gene for a myosin heavy-chain in Caenorhabditis elegans. J Mol Biol 1977; 114:133–140.PubMedGoogle Scholar
  45. 45.
    Doi M, Iwasaki K. Regulation of retrograde signaling at neuromuscular junctions by the novel C2 domain protein AEX-1. Neuron 2002; 33:249–259.PubMedGoogle Scholar
  46. 46.
    Jacob TC, Kaplan JM. The EGL-21 carboxypeptidase E facilitates acetylcholine release at Caenorhabditis elegans neuromuscular junctions. J Neurosci 2003; 23:2122–2130.PubMedGoogle Scholar
  47. 47.
    Eipper BA, Milgram SL, Husten EJ et al. Peptidylglycine alpha-amidating monooxygenase: a multifunctional protein with catalytic, processing and routing domains. Protein Sci 1993; 2:489–497.PubMedGoogle Scholar
  48. 48.
    Han M, Park D, Vanderzalm PJ et al. Drosophila uses two distinct neuropeptide amidating enzymes, dPAL1 and dPAL2. J Neurochem 2004; 90:129–141.PubMedGoogle Scholar
  49. 49.
    Hall DH, Hedgecock EM. Kinesin-related gene unc-104 is required for axonal transport of synaptic vesicles in C. elegans. Cell 1991; 65:837–847.PubMedGoogle Scholar
  50. 50.
    Schinkmann K. FMRFamide-like peptides in the nematodes Caenorhabditis elegans and Caenorhabditis vulgaris. PhD thesis, Boston, MA: Boston University 1994.Google Scholar
  51. 51.
    Zahn TR, Angleson JK, MacMorris MA et al. Dense core vesicle dynamics in Caenorhabditis elegans neurons and the role of kinesin UNC-104. Traffic 2004; 5:544–559.PubMedGoogle Scholar
  52. 52.
    Salio C, Lossi L, Ferrini F et al. Neuropeptides as synaptic transmitters. Cell Tissue Res 2006; 326:583–598.PubMedGoogle Scholar
  53. 53.
    Bonanomi D, Benfenati F, Valtorta F. Protein sorting in the synaptic vesicle life cycle. Progress in Neurobiology 2006; 80:177–217.PubMedGoogle Scholar
  54. 54.
    Ahmed S, Maruyama IN, Kozma R et al. The Caenorhabditis elegans unc-13 gene product is a phospholipid-dependent high-affinity phorbol ester receptor. Biochem J 1992; 287:995–999.PubMedGoogle Scholar
  55. 55.
    Richmond JE, Davis WS, Jorgensen EM. UNC-13 is required for synaptic vesicle fusion in C. elegans. Nat Neurosci 1999; 2:959–964.PubMedGoogle Scholar
  56. 56.
    Sieburth D, Madison JM, Kaplan JM. PKC-1 regulates secretion of neuropeptides. Nat Neurosci 2007; 10:49–57.PubMedGoogle Scholar
  57. 56a.
    Hammerlund M, Watanabe S, Schuske K et al. CAPS and syntaxin dock dense core vesicles to the plasma membrane in neurons. J Cell Biol 2008; 180:483–491.Google Scholar
  58. 57.
    Kohn RE, Duerr JS, McManus JR et al. Expression of multiple UNC-13 proteins in the Caenorhabditis elegans nervous system. Molecular biology of the cell 2000; 11:3441–3452.PubMedGoogle Scholar
  59. 58.
    Ann K, Kowalchyk JA, Loyet KM et al. Novel Ca2+-binding protein (CAPS) related to UNC-31 required for Ca2+-activated exocytosis. J Biol Chem 1997; 272:19637–19640.PubMedGoogle Scholar
  60. 58a.
    Speese S, Petrie M, Schuske K et al. UNC-31 (CAPS) is required for dense-core vesicle but not synaptic vesicle exocytosis in Caenorhabditis elegans. J Neurosci 2007; 27:6150–6162.PubMedGoogle Scholar
  61. 59.
    Cai T, Fukushige T, Notkins AL et al. Insulinoma-Associated Protein IA-2, a vesicle transmembrane protein, genetically interacts with UNC-31/CAPS and affects Neurosecretion in Caenorhabditis elegans. J Neurosci 2004; 24:3115–3124.PubMedGoogle Scholar
  62. 60.
    Grishanin RN, Klenchin VA, Loyet KM et al. Membrane association domains in Ca2+-dependent activator protein for secretion mediate plasma membrane and dense-core vesicle binding required for Ca2+-dependent exocytosis. J Biol Chem 2002; 277:22025–22034.PubMedGoogle Scholar
  63. 61.
    Renden R, Berwin B, Davis W et al. Drosophila CAPS is an essential gene that regulates dense-core vesicle release and synaptic vesicle fusion. Neuron 2001; 31:421–437.PubMedGoogle Scholar
  64. 62.
    Fares H, Grant B. Deciphering endocytosis in Caenorhabditis elegans. Traffic 2002; 3:11–19.PubMedGoogle Scholar
  65. 63.
    Rosoff ML, Doble KE, Price DA et al. The FLP-1 propeptide is processed into multiple, highly similar FMRFamide-like peptides in Caenorhabditis elegans. Peptides 1993; 14:331–338.PubMedGoogle Scholar
  66. 64.
    Husson SJ, Schoofs L. Altered neuropeptide profile of Caenorhabditis elegans lacking the chaperone protein 7B2 as analyzed by mass spectrometry. FEBS Lett 2007; 581:4288–4292.PubMedGoogle Scholar
  67. 65.
    Cowden C, Stretton AO. AF2, an Ascaris neuropeptide: isolation, sequence and bioactivity. Peptides 1993; 14:423–430.PubMedGoogle Scholar
  68. 66.
    Cowden C, Stretton AO. Eight novel FMRFamide-like neuropeptides isolated from the nematode Ascaris suum. Peptides 1995; 16:491–500.PubMedGoogle Scholar
  69. 67.
    Cowden C, Stretton AO, Davis RE. AF1, a sequenced bioactive neuropeptide isolated from the nematode Ascaris suum. Neuron 1989; 2:1465–1473.PubMedGoogle Scholar
  70. 68.
    Yew JY, Kutz KK, Dikler S et al. Mass spectrometric map of neuropeptide expression in Ascaris suum. J Comp Neurol 2005; 488:396–413.PubMedGoogle Scholar
  71. 69.
    Keating CD, Holden-Dye L, Thorndyke MC et al. The FMRFamide-like neuropeptide AF2 is present in the parasitic nematode Haemonchus contortus. Parasitology 1995; 111 ( Pt 4), 515–521.PubMedGoogle Scholar
  72. 70.
    Marks NJ, Sangster NC, Maule AG et al. Structural characterisation and pharmacology of KHEYLRFamide (AF2) and KSAYMRFamide (PF3/AF8) from Haemonchus contortus. Mol Biochem Parasitol 1999; 100:185–194.PubMedGoogle Scholar
  73. 71.
    Geary TG, Price DA, Bowman JW et al. Two FMRFamide-like peptides from the free-living nematode Panagrellus redivivus. Peptides 1992; 13:209–214.PubMedGoogle Scholar
  74. 72.
    Maule AG, Geary TG, Bowman JW et al. Inhibitory effects of nematode FMRFamide-related peptides (FaRPs) on muscle strips from Ascaris suum. Invert Neurosci 1995; 1:255–265.PubMedGoogle Scholar
  75. 73.
    Maule AG, Shaw C, Bowman JW et al. The FMRFamide-like neuropeptide AF2 (Ascaris suum) is present in the free-living nematode, Panagrellus redivivus (Nematoda, Rhabditida). Parasitology 1994; 109 (Pt 3):351–356.PubMedGoogle Scholar
  76. 74.
    Maule AG, Shaw C, Bowman JW et al. KSAYMRFamide: a novel FMRFamide-related heptapeptide from the free-living nematode, Panagrellus redivivus, which is myoactive in the parasitic nematode, Ascaris suum. Biochem Biophys Res Commun 1994; 200:973–980.PubMedGoogle Scholar
  77. 75.
    Simmer F, Tijsterman M, Parrish S et al. Loss of the putative RNA-directed RNA polymerase RRF-3 makes C. elegans hypersensitive to RNAi. Curr Biol 2002; 12:1317–1319.PubMedGoogle Scholar
  78. 76.
    Schmitz C, Kinge P, Hutter H. Axon guidance genes identified in a large-scale RNAi screen using the RNAi-hypersensitive Caenorhabditis elegans strain nre-1(hd20) lin-15b(hd126). Proc Natl Acad Sci USA 2007; 104:834–839.PubMedGoogle Scholar
  79. 76a.
    Tavernarakis N, Wang SL, Dorovkov M et al. Heritable and inducible genetic interference by doublestranded RNA encoded by transgenes. Nat Genet 2000; 24:180–183.PubMedGoogle Scholar
  80. 77.
    Cassada RC, Russell RL. The dauerlarva, post-embryonic developmental variant of the nematode Caenorhabditis elegans. Dev Biol 1975; 46:326–342.PubMedGoogle Scholar
  81. 78.
    Johnson TE, Mitchell DH, Kline S et al. Arresting development arrests aging in the nematode Caenorhabditis elegans. Mechanisms of ageing and development 1984; 28:23–40.PubMedGoogle Scholar
  82. 79.
    Riddle DL, Albert PS. Genetic and environmental regulation of dauer larva development. In: Riddle DL, Blumenthal T, Meyer BJ, Priess JR, eds. C. elegans II. New York: Cold Spring Harbor Laboratory Press, 1997:739–768.Google Scholar
  83. 80.
    Thomas JH, Birnby DA, Vowels JJ. Evidence for parallel processing of sensory information controlling dauer formation in Caenorhabditis elegans. Genetics 1993; 134:1105–1117.PubMedGoogle Scholar
  84. 81.
    Kao G, Nordenson C, Still M et al. ASNA-1 positively regulates insulin secretion in C. elegans and mammalian cells. Cell 2007; 128:577–587.PubMedGoogle Scholar
  85. 82.
    Kenyon C, Chang J, Gensch E et al. A C. elegans mutant that lives twice as long as wild type. Nature 1993; 366:461–464.PubMedGoogle Scholar
  86. 83.
    Gems D, Sutton AJ, Sundermeyer ML et al. Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans. Genetics 1998; 150:129–155.PubMedGoogle Scholar
  87. 84.
    Dlakic M. A new family of putative insulin receptor-like proteins in C. elegans. Curr Biol 2002; 12: R155–157.PubMedGoogle Scholar
  88. 85.
    Bargmann CI, Horvitz HR. Control of larval development by chemosensory neurons in Caenorhabditis elegans. Science 1991; 251:1243–1246.PubMedGoogle Scholar
  89. 86.
    Malone EA, Thomas JH. A screen for nonconditional dauer-constitutive mutations in Caenorhabditis elegans. Genetics 1994; 136:879–886.PubMedGoogle Scholar
  90. 87.
    Kodama E, Kuhara A, Mohri-Shiomi A et al. Insulin-like signaling and the neural circuit for integrative behavior in C. elegans. Genes Dev 2006; 20:2955–2960.PubMedGoogle Scholar
  91. 88.
    Hedgecock EM, Russell RL. Normal and mutant thermotaxis in the nematode Caenorhabditis elegans. Proc Natl Acad Sci USA 1975; 72:4061–4065.PubMedGoogle Scholar
  92. 89.
    Mori I, Ohshima Y. Neural regulation of thermotaxis in Caenorhabditis elegans. Nature 1995; 376:344–348.PubMedGoogle Scholar
  93. 90.
    Sawin ER, Ranganathan R, Horvitz HR. C. elegans locomotory rate is modulated by the environment through a dopaminergic pathway and by experience through a serotonergic pathway. Neuron 2000; 26:619–631.PubMedGoogle Scholar
  94. 91.
    White JG, Southgate E, Thomson JN et al. The structure of the nervous system of the nematode Caenorhabditis elegans. Philos Trans R Soc Lond B Biol Sci 1986; 314:1–340.Google Scholar
  95. 92.
    Ward S. Chemotaxis by the nematode Caenorhabditis elegans: identification of attractants and analysis of the response by use of mutants. Proc Natl Acad Sci USA 1973; 70:817–821.PubMedGoogle Scholar
  96. 93.
    Saeki S, Yamamoto M, Iino Y. Plasticity of chemotaxis revealed by paired presentation of a chemoattractant and starvation in the nematode Caenorhabditis elegans. J Exp Biol 2001; 204:1757–1764.PubMedGoogle Scholar
  97. 94.
    Tomioka M, Adachi T, Suzuki H et al. The insulin/PI 3-kinase pathway regulates salt chemotaxis learning in Caenorhabditis elegans. Neuron 2006; 51:613–625.PubMedGoogle Scholar
  98. 95.
    Schinkmann K, Li C. Localization of FMRFamide-like peptides in Caenorhabditis elegans. J Comp Neurol 1992; 316:251–260.PubMedGoogle Scholar
  99. 96.
    Nelson LS, Rosoff ML et al. Disruption of a neuropeptide gene, flp-1, causes multiple behavioral defects in Caenorhabditis elegans. Science 1998; 281:1686–1690.PubMedGoogle Scholar
  100. 96a.
    Ringstad N, Horvitz HR FMRFamide neuropeptides and acetylcholine synergistically inhibit egg-laying by C. elegans. Nature Neuroscience 2008; 11:1168–1176.PubMedGoogle Scholar
  101. 97.
    Alfonso A, Grundahl K, Duerr JS et al. The Caenorhabditis elegans unc-17 gene: a putative vesicular acetylcholine transporter. Science 1993; 261:617–619.PubMedGoogle Scholar
  102. 98.
    McIntire SL, Jorgensen E, Kaplan J et al. The GABAergic nervous system of Caenorhabditis elegans. Nature 1993; 364:337–341.PubMedGoogle Scholar
  103. 99.
    Brenner S. The genetics of Caenorhabditis elegans. Genetics 1974; 77:71–94.PubMedGoogle Scholar
  104. 100.
    Duerr JS, Gaskin J et al. Identified neurons in C. elegans coexpress vesicular transporters for acetylcholine and monoamines. American J Physiology 2001; 280:C1616–1622.Google Scholar
  105. 101.
    Waggoner LE, Hardaker LA, Golik S et al. Effect of a neuropeptide gene on behavioral states in Caenorhabditis elegans egg-laying. Genetics 2000; 154:1181–1192.PubMedGoogle Scholar
  106. 101a.
    Cohen M, Reale V, Olofsson B et al. Coordinated regulation of foraging and metabolism in C. elegans by RFfamide neuropeptide signaling. Cell Metab 2009; 9:375–385.PubMedGoogle Scholar
  107. 101b.
    Janssen T, Husson SJ, Lindemans M et al. Functional characterization of three G protein-coupled receptors for pigment dispersing factors in Caenorhabditis elegans. J Biol Chem 2008; 283:15241–15249.PubMedGoogle Scholar
  108. 101c.
    Park SK, Link CD, Johnson TE Life-span extension by dietary restriction is mediated by NLP-7 signaling and coelomocyte endocytosis in C. elegans. FASEB J 2009. [Epub ahead of print].Google Scholar
  109. 101d.
    Muir RE, Tan M-W. Virulence of Leucobacter chromiireducens subsp. solipictus to Caenorhabditis elegans: Characterization of a novel host-pathogen interaction. Appl Environ Microbiol 2008; 74:4185–4198.PubMedGoogle Scholar
  110. 101e.
    Pujol N, Cypowyu S, Ziegler K et al. Distinct innate immune responses to infection and wounding in the C. elegans epidermis. Curr Biol 2008; 18:481–489.PubMedGoogle Scholar
  111. 101f.
    Styer KL, Singh V, Macosko E et al. Innate immunity in Caenorhabditis elegans is regulated by neurons expressing NPR-1/GPCR. Science 2008; 322:460–464.PubMedGoogle Scholar
  112. 101g.
    Janssen T, Husson SJ, Meelkop E et al. Discovery and characterization of a conserved pigment dispersing factor-like neuropeptide pathway in Caenorhabditis elegans. J Neurochem 2009; 111:228–41.PubMedGoogle Scholar
  113. 101h.
    Husson SJ, Janssen T, Baggerman G et al. Impaired processing of FLP and NLP peptides in carboxypeptidase E (EGL-21)-deficient Caenorhabditis elegans as analyzed by mass spectrometry. J Neurochem 2007; 102:246–60.PubMedGoogle Scholar
  114. 101i.
    Lindemans M, Janssen T, Husson SJ et al. A neuromedin-pyrokinin-like neuropeptide signaling system in Caenorhabditis elegans. Biochem Biophys Res Commun 2009; 379:760–764.PubMedGoogle Scholar
  115. 101j.
    McVeigh P, Alexander-Bowman S, Veal E et al. Neuropeptide-like protein diversity in phylum Nematoda. Int J Parasitol 2008; 38:1493–1503.Google Scholar
  116. 102.
    Nguyen M, Alfonso A, Johnson CD et al. Caenorhabditis elegans mutants resistant to inhibitors of acetylcholinesterase. Genetics 1995; 140:527–535.PubMedGoogle Scholar
  117. 103.
    Robertson HM. Two large families of chemoreceptor genes in the nematodes Caenorhabditis elegans and Caenorhabditis briggsae reveal extensive gene duplication, diversification, movement and intron loss. Genome Research 1998; 8:449–463.PubMedGoogle Scholar
  118. 104.
    Robertson HM. The large srh family of chemoreceptor genes in Caenorhabditis nematodes reveals processes of genome evolution involving large duplications and deletions and intron gains and losses. Genome Research 2000; 10:192–203.PubMedGoogle Scholar
  119. 105.
    Robertson HM. Updating the str and srj (stl) families of chemoreceptors in Caenorhabditis nematodes reveals frequent gene movement within and between chromosomes. Chem Senses 2001; 26:151–159.PubMedGoogle Scholar
  120. 106.
    Bargmann CI. Neurobiology of the Caenorhabditis elegans genome. Science 1998; 282:2028–2033.PubMedGoogle Scholar
  121. 107.
    Keating CD, Kriek N, Daniels M et al. Whole-genome analysis of 60 G protein-coupled receptors in Caenorhabditis elegans by gene knockout with RNAi. Curr Biol 2003; 13:1715–1720.PubMedGoogle Scholar
  122. 108.
    Bonini JA, Jones KA, Adham N et al Identification and characterization of two G protein-coupled receptors for neuropeptide FF. J Biol Chem 2000; 275:39324–39331.PubMedGoogle Scholar
  123. 109.
    Cazzamali G, Grimmelikhuijzen CJ. Molecular cloning and functional expression of the first insect FMRFamide receptor. Proc Natl Acad Sci USA 2002; 99:12073–12078.PubMedGoogle Scholar
  124. 110.
    Duttlinger A, Mispelon M, Nichols R. The structure of the FMRFamide receptor and activity of the cardioexcitatory neuropeptide are conserved in mosquito. Neuropeptides 2003; 37:120–126.PubMedGoogle Scholar
  125. 111.
    Meeusen T, Mertens I, Clynen E et al. Identification in Drosophila melanogaster of the invertebrate G protein-coupled FMRFamide receptor. Proc Natl Acad Sci USA 2002; 99:15363–15368.PubMedGoogle Scholar
  126. 112.
    Tensen CP, Cox KJ, Smit AB et al. The lymnaea cardioexcitatory peptide (LyCEP) receptor: a G-protein-coupled receptor for a novel member of the RFamide neuropeptide family. J Neurosci 1998; 18:9812–9821.PubMedGoogle Scholar
  127. 113.
    Lingueglia E, Champigny G, Lazdunski M et al. Cloning of the amiloride-sensitive FMRFamide peptide-gated sodium channel. Nature 1995; 378:730–733.PubMedGoogle Scholar
  128. 114.
    Kubiak TM, Larsen MJ, Nulf SC et al. Differential activation of “social” and “solitary” variants of the Caenorhabditis elegans G protein-coupled receptor NPR-1 by its cognate ligand AF9. J Biol Chem 2003; 278:33724–33729.PubMedGoogle Scholar
  129. 115.
    Kubiak TM, Larsen MJ, Zantello MR et al. Functional annotation of the putative orphan Caenorhabditis elegans G-protein-coupled receptor C10C6.2 as a FLP15 peptide receptor. J Biol Chem 2003; 278:42115–42120.PubMedGoogle Scholar
  130. 116.
    Lowery DE, Geary TG, Kubiak TM et al. G protein-coupled receptor-like receptors and modulators thereof. (United States: Pharmacia & Upjohn Company) 2003.Google Scholar
  131. 117.
    Mertens I, Meeusen T, Janssen T et al. Molecular characterization of two G protein-coupled receptor splice variants as FLP2 receptors in Caenorhabditis elegans. Biochem Biophys Res Commun 2005; 330:967–974.PubMedGoogle Scholar
  132. 118.
    Mertens I, Vandingenen A, Meeusen T et al. Functional characterization of the putative orphan neuropeptide G-protein coupled receptor C26F1.6 in Caenorhabditis elegans. FEBS Lett 2004; 573:55–60.PubMedGoogle Scholar
  133. 119.
    Mertens I, Clinckspoor I, Janssen T et al. FMRFamide related peptide ligands activate the Caenorhabditis elegans orphan GPCR Y59H11AL.1. Peptides 2006; 27:1291–1296.PubMedGoogle Scholar
  134. 120.
    de Bono M, Bargmann CI. Natural variation in a neuropeptide Y receptor homolog modifies social behavior and food response in C. elegans. Cell 1998; 94:679–689.PubMedGoogle Scholar
  135. 121.
    Davies AG, Bettinger JC, Thiele TR et al. Natural variation in the npr-1 gene modifies ethanol responses of wild strains of C. elegans. Neuron 2004; 42:731–743.PubMedGoogle Scholar
  136. 122.
    Cheung BH, Arellano-Carbajal F, Rybicki I et al. Soluble guanylate cyclases act in neurons exposed to the body fluid to promote C. elegans aggregation behavior. Curr Biol 2004; 14:1105–1111.PubMedGoogle Scholar
  137. 123.
    Morton DB, Hudson ML, Waters E et al. Soluble guanylyl cyclases in Caenorhabditis elegans: NO is not the answer. Curr Biol 1999; 9:R546–547.PubMedGoogle Scholar
  138. 124.
    Gray JM, Karow DS, Lu H et al. Oxygen sensation and social feeding mediated by a C. elegans guanylate cyclase homologue. Nature 2004; 430:317–322.PubMedGoogle Scholar
  139. 125.
    Rogers C, Reale V, Kim K et al. Inhibition of Caenorhabditis elegans social feeding by FMRFamide-related peptide activation of NPR-1. Nat Neurosci 2003; 6:1178–1185.PubMedGoogle Scholar
  140. 126.
    Dossey AT, Reale V, Chatwin H et al. NMR analysis of Caenorhabditis elegans FLP-18 neuropeptides: implications for NPR-1 activation. Biochemistry 2006; 45:7586–7597.PubMedGoogle Scholar
  141. 127.
    Papaioannou S, Marsden D, Franks CJ et al. Role of a FMRFamide-like family of neuropeptides in the pharyngeal nervous system of Caenorhabditis elegans. J Neurobiol 2005; 65:304–319.PubMedGoogle Scholar
  142. 128.
    Rogers CM, Franks CJ, Walker RJ et al. Regulation of the pharynx of Caenorhabditis elegans by 5-HT, octopamine and FMRFamide-like neuropeptides. J Neurobiol 2001; 49:235–244.PubMedGoogle Scholar
  143. 129.
    Cowden C, Sithigorngul P, Brackley P et al. Localization and differential expression of FMRFamide-like immunoreactivity in the nematode Ascaris suum. J Comp Neurol 1993; 333:455–468.PubMedGoogle Scholar
  144. 130.
    McVeigh P, Geary TG, Marks NJ et al. The FLP-side of nematodes. Trends Parasitol 2006; 22:385–396.PubMedGoogle Scholar
  145. 131.
    Bowman JW, Friedman AR, Thompson DP et al. Structure-activity relationships of an inhibitory nematode FMRFamide-related peptide, SDPNFLRFamide (PF1), on Ascaris suum muscle. Int J Parasitol 2002; 32:1765–1771.PubMedGoogle Scholar
  146. 132.
    Fellowes RA, Maule AG, Marks NJ et al. Modulation of the motility of the vagina vera of Ascaris suum in vitro by FMRF amide-related peptides. Parasitology 1998; 116:(Pt 3)277–287.PubMedGoogle Scholar
  147. 133.
    Moffett CL, Beckett AM, Mousley A et al. The ovijector of Ascaris suum: multiple response types revealed by Caenorhabditis elegans FMRFamide-related peptides. Int J Parasitol 2003; 33:859–876.PubMedGoogle Scholar
  148. 134.
    Trailovic SM, Clark CL, Robertson AP et al. Brief application of AF2 produces long lasting potentiation of nAChR responses in Ascaris suum. Mol Biochem Parasitol 2005; 139:51–64.PubMedGoogle Scholar
  149. 135.
    Brownlee D, Holden-Dye L, Walker R. The range and biological activity of FMRFamide-related peptides and classical neurotransmitters in nematodes. Adv Parasitol 2000; 45:109–180.PubMedGoogle Scholar
  150. 136.
    Brownlee DJ, Fairweather I. Exploring the neurotransmitter labyrinth in nematodes. Trends Neurosci 1999; 22:16–24.PubMedGoogle Scholar
  151. 137.
    Day TA, Maule AG. Parasitic peptides! The structure and function of neuropeptides in parasitic worms. Peptides 1999; 20:999–1019.PubMedGoogle Scholar
  152. 138.
    Bowman JW, Friedman AR, Thompson DP et al. Structure-activity relationships of KNEFIRFamide (AF1), a nematode FMRFamide-related peptide, on Ascaris suum muscle. Peptides 1996; 17:381–387.PubMedGoogle Scholar
  153. 139.
    Davis RE, Stretton AO. Structure-activity relationships of 18 endogenous neuropeptides on the motor nervous system of the nematode Ascaris suum. Peptides 2001; 22:7–23.PubMedGoogle Scholar
  154. 140.
    Kimber MJ, McKinney S, McMaster S et al. flp gene disruption in a parasitic nematode reveals motor dysfunction and unusual neuronal sensitivity to RNA interference. FASEB J 2007; 21:1233–1243.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  1. 1.Chris Li-Department of BiologyCity College of the City University of New YorkNew York
  2. 2.Department of BiologyBrandeis UniversityWalthamUSA

Personalised recommendations