Role of a FMRFamide-like family of neuropeptides in the pharyngeal nervous system of Caenorhabditis elegans
Sylvana Papaioannou
Neurosciences Research Group, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, United Kingdom, SO16 7PX
Search for more papers by this authorDavid Marsden
Neurosciences Research Group, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, United Kingdom, SO16 7PX
Search for more papers by this authorChristopher J. Franks
Neurosciences Research Group, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, United Kingdom, SO16 7PX
Search for more papers by this authorRobert J. Walker
Neurosciences Research Group, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, United Kingdom, SO16 7PX
Search for more papers by this authorCorresponding Author
Lindy Holden-Dye
Neurosciences Research Group, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, United Kingdom, SO16 7PX
Neurosciences Research Group, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, United Kingdom, SO16 7PXSearch for more papers by this authorSylvana Papaioannou
Neurosciences Research Group, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, United Kingdom, SO16 7PX
Search for more papers by this authorDavid Marsden
Neurosciences Research Group, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, United Kingdom, SO16 7PX
Search for more papers by this authorChristopher J. Franks
Neurosciences Research Group, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, United Kingdom, SO16 7PX
Search for more papers by this authorRobert J. Walker
Neurosciences Research Group, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, United Kingdom, SO16 7PX
Search for more papers by this authorCorresponding Author
Lindy Holden-Dye
Neurosciences Research Group, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, United Kingdom, SO16 7PX
Neurosciences Research Group, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, United Kingdom, SO16 7PXSearch for more papers by this authorAbstract
The nervous system of C. elegans has a remarkable abundance of flp genes encoding FMRFamide-like (FLP) neuropeptides. To provide insight into the physiological relevance of this neuropeptide diversity, we have tested more than 30 FLPs (encoded by 23 flps) for bioactivity on C. elegans pharynx. Eleven flp genes encode peptides that inhibit pharyngeal activity, while eight flp genes encode peptides that are excitatory. Three potent peptides (inhibitory, FLP-13A, APEASPFIRFamide; excitatory, FLP-17A, KSAFVRFamide; excitatory, FLP-17B, KSQYIRFamide) are encoded by flp genes, which, according to reporter gene constructs, are expressed in pharyngeal motoneurons. Thus, they may act through receptors localized on the pharyngeal muscle. The two other potent peptides, FLP-8 (excitatory AF1, KNEFIRFamide,) and FLP-11A (inhibitory, AMRNALVRFamide), appear to be expressed in extrapharyngeal neurons and are therefore likely to act either indirectly or as neurohormones. Intriguingly, a single neuron can express peptides that have potent but opposing biological activity in the pharynx. Only five flp genes encode neuropeptides that have no observable effect on the pharynx, but none of these have shown reporter gene expression in the pharyngeal nervous system. To examine the roles of multiple peptides produced from single precursors, a comparison was made between the bioactivity of different neuropeptides for five flp genes (flp-3, flp-13, flp-14, flp-17, and flp-18). For all but one gene (flp-14), the effects of peptides encoded by the same gene were similar. Overall, this study demonstrates the impressive neurochemical complexity of the simple circuit that regulates feeding in the nematode, C. elegans. © 2005 Wiley Periodicals, Inc. J Neurobiol, 2005
REFERENCES
- Albertson DG, Thomson JN. 1976. The pharynx of Caenorhabditis elegans. Phil Trans R Soc Lond B 275: 299–325.
- Avery L. 1993. Motor-neuron M3 controls pharyngeal muscle-relaxation timing in Caenorhabditis elegans. J E Biol 175: 283–297.
- Avery L, Horvitz R. 1989. Pharyngeal pumping continues after laser killing of the pharyngeal nervous system of C. elegans. Neuron 3: 473–485.
- Avery L, Raizen D, Lockery S. 1995. Electrophysiological methods. Meth Cell Biol 48: 251–269.
- Avery L, Thomas J. 1997. Feeding and Defecation. In: D Riddle, T Blumenthal, BJ Meyer, J Preiss, editors. C. elegans II. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, pp 679–716.
- Bowman JW, Friedman AR, Thompson DP, Ichpurani AK, Kellman MF, Marks N, Maule AG, Geary TG. 1996. Structure-activity relationships of KNEFIRFamide (AF1), a nematode FMRFamide-related peptide, on Ascaris muscle. Peptides 17: 381–387.
- Brenner S. 1974. The genetics of Caenorhabditis elegans. Genetics 77: 71–94.
- Brockie PJ, Mellem JE, Hills T, Masden DM, Maricq AV. 2001. The C. elegans glutamate receptor subunit NMR-1 is required for slow NMDA-activated currents that regulate reversal frequency during locomotion. Neuron 31: 617–630.
- Brownlee DJA, Brennan GP, Halton DW, Fairweather I, Shaw C. 1994. Ultrastructural localization of pancreatic polypeptide and FMRFamide-like immunoreactivites within the central nervous system of the nematode Ascaris suum. Parasitology 108: 587–593.
- Brownlee DJA, Fairweather I, Thorndyke MC, Johnston CF. 1996. Cellular and subcellular-localization of SALMFamide (S1)-like immunoreactivity within the central-nervous-system of the nematode Ascaris suum (Nematoda, Ascaroidea). Parasitol Res 82: 149–156.
- Cowden C, Stretton AW. 1993. AF2, an Ascaris neuropeptide—isolation, sequence, and bioactivity. Peptides 14: 423–430.
- Cowden C, Stretton AW, Davis RE. 1989. AF1, a sequenced bioactive neuropeptide isolated from the nematode Ascaris suum. Neuron 2: 1465–1473.
- Davis R, Stretton A. 2001. Structure-activity relationships of 18 endogenous neuropeptides on the motornervous system of the nematode Ascaris suum. Peptides 22: 7–23.
- Davis RE, Stretton AW. 1996. The motornervous system of Ascaris: Electrophysiology and anatomy of the neurons and their control by neuromodulators. Parasitology 113: S97–S117.
- Dent JA, Davis MW, Avery L. 1997. avr-15 encodes a chloride channel subunit that mediates inhibitory glutamatergic neurotransmission and ivermectin sensitivity in Caenorhabditis elegans. EMBO J 16: 5867–5879.
- Fellowes RA, Maule AG, Marks NJ, Geary TG, Thompson DP, Halton DW. 2000. Nematode neuropeptide modulation of the vagina vera muscle of Ascaris suum in vitro. Parasitology 120: 78–89.
- Franks CJ, Pemberton D, Vinogradova I, Walker RJ, Holden-Dye L. 2002. The ionic basis of the resting membrane potential and action potential in the pharyngeal muscle of Caenorhabditis elegans. J Neurophysiol 87: 954–961.
- Geary TG, Price DA, Bowman JW, Winterowd CA, Mackenzie CD, Garrison RD, Williams JF, Freiedman AR. 1992. Two FMRFamide-like peptides from the free-living nematode Panagrellus redivivus. Peptides 13: 209–214.
- Graham MK, Fairweather I, McGowan JG. 1997. The effect of FaRPs on the motility of isolated muscle strips from the liver fluke Fasciola hepatica. Parasitology 114: 455–465.
- Hobson RT, Geng J, Gray AD, Komuniecki RW. 2003. Ser-7b, a constitutively active G alpha coupled 5-HT7 like receptor expressed in the Caenorhabditis elegans M4 pharynx motorneuron. J Neurochem 87: 22–29.
- Horvitz HR, Chalfie M, Sulston JE, Evans PD. 1982. Serotonin and octopamine in the nematode C. elegans. Science 216: 1012–1014.
- Johnston RN, Shaw C, Halton DW, Verhaert P, Blair KL, Brennan GP, Price DA, Anderson PAV. 1996. Isolation, localization, and bioactivity of the FMRFamide- related neuropeptides GYIRFamide and YIRFamide from the marine turbellarian Bdelloura candida. J Neurochem 67: 814–821.
- Keating CD, Holden-Dye L, Thorndyke MC, Williams RG, Mallett A, Walker RJ. 1995. The FMRFamide-like neuropeptide AF2 is present in the parasitic nematode Haemonchus contortus. Parasitology 111: 515–521.
- Keating CD, Kriek N, Daniels M, Ashcroft NR, Hopper NA, Siney EJ, Holden-Dye L, Burke JF. 2003. Whole-genome analysis of 60 G protein-coupled receptors in Caenorhabditis elegans by gene knockout with RNAi. Curr Biol 13: 1715–1720.
- Kim K, Li C. 2004. Expression and regulation of an FMRFamide-related neuropeptide gene family in Caenorhabditis elegans. J Comp Neurol 475: 540–550.
- Kubiak TM, Larsen MJ, Nulf SC, Zantello MR, Buston KJ, Bowman JW, Modric T, Lowery DE. 2003a. Differential activation of “social” and “solitary” variants of the C. elegans GPCR NPR-1 by its cognate ligand AF9. J Biol Chem 278: 33724–33729.
- Kubiak TM, Larsen MJ, Zantello MR, Bowman JW, Nulf SC, Lowery DE. 2003b. Functional annotation of the putative orphan Caenorhabditis elegans G protein-coupled receptor C10C6.2 as a FLP15 peptide receptor. J Biol Chem 278: 42115–42120.
- Lee RYN, Chalfie M, Horvitz HR, Avery L. 1999. EAT-4, a homolog of a mammalian sodium-dependent inorganic phosphate co-transporter, is necessary for glutamatergic neurotransmission in Caenorhabditis elegans. J Neurosci 19: 159–167.
- Li C, Kim K, Nelson LS. 1999a. FMRFamide-related neuropeptide gene family in Caenorhabditis elegans. Brain Res 848: 26–34.
- Li C, Nelson LS, Kim K, Nathoo A, Hart AC. 1999b. Neuropeptide gene families in the nematode Caenorhabditis elegans. Ann NY Acad Sci USA 897: 239–252.
- Li HY, Avery L, Denk W, Hess GP. 1997. Identification of chemical synapses in the pharynx of Caenorhabditis elegans. Proc Natl Acad Sci USA 94: 5912–5916.
- Marks NJ, Maule AG, Geary TG, Thompson DP, Davis JP, Halton DW, Verhaert P, Shaw C. 1997. APEASPFIRFamide,a novel FMRFamide-related decapeptide from Caenorhabditis elegans: Structure and myoactivity. Biochem Biophys Res Comm 231: 591–595.
- Marks NJ, Maule AG, Geary TG, Thompson DP, Li C, Halton DW, Shaw C. 1998. KSAYMRFamide (PF3/AF8) is present in the free-living nematode,Caenorhabditis elegans. Biochem Biophys Res Comm 248: 422–425.
- Marks NJ, Shaw C, Halton DW, Thompson DP, Geary TG, Li C, Maule AG. 2001. Isolation and preliminary biological assessment of AADGAPLIRFamide and SVPGVLRFamide from C. elegans. Biochem Biophys Res Comm 286: 1170–1176.
- Marks NJ, Shaw C, Maule AG, Davis JP, Halton DW, Verhaert P, Geary TG, Thompson DP. 1995. Isolation of AF2 (KHEYLRFamide) from Caenorhabditis elegans: Evidence for the presence of more than one FMRFamide related peptide-encoding gene. Biochem Biophys Res Comm 217: 845–851.
- Mertens I, Meeusen T, Janssen T, Nachmann R, Schoofs L. 2005. Molecular characterization of two G-protein coupled receptor splice variants as FLP2 receptors in Caenorhabditis elegans. Biochem Biophys Res Comm 330: 967–974.
- Mertens I, Vandingenen A, Meeusen T, Janssen T, Luyten W, Nachmann RJ, De Loof A, Schoofs L. 2004. Functional characterization of the putative orphan G-protein coupled receptor C26F1.6 in Caenorhabditis elegans. FEBS Lett 573: 55–60.
- Nathoo AN, Moeller RA, Westlund BA, Hart AC. 2001. Identification of neuropeptide-like protein gene families in Caenorhabditis elegans and other species. Proc Natl Acad Sci USA 98: 14000–14005.
- Nelson LS, Kim KY, Memmott RE, Li C. 1998a. FMRFamide-related gene family in the nematode, Caenorhabditis elegans. Mol Brain Res 58: 103–111.
- Nelson LS, Rosoff ML, Li C. 1998b. Disruption of a neuropeptide gene, flp-1, causes multiple behavioral defects in Caenorhabditis elegans. Science 281: 1686–1690.
- Niacaris T, Avery L. 2003. Serotonin regulates repolarization of the C. elegans pharyngeal muscle. J Exp Biol 206: 223–231.
- Nonet ML, Saifee O, Zhao HJ, Rand JB, Wei LP. 1998. Synaptic transmission deficits in Caenorhabditis elegans synaptobrevin mutants. J Neurosci 18: 70–80.
- Parkinson J, Mitreva M, Whitton C, Thomson M, Daub J, Martin J, Schmid R, Hall N, Barrell B, Waterston RH, et al. 2004. A transcriptome analysis of the phylum nematoda. Nature Gen 36: 1259–1267.
- Price DA. 1986. Evolution of a molluscan cardioregulatory peptide. Am Zool 26: 1007–1015.
- Price DA, Greenberg MJ. 1977. Structure of a molluscan cardioregulatory neuropeptide. Science 197: 670–671.
- Raizen DM, Lee RN, Avery L. 1995. Interacting genes required for pharyngeal excitation by motor-neuron MC in Caenorhabditis elegans. Genetics 141: 1365–1382.
- Rand JB, Duerr JS, Frsiby DL. 2000. Neurogenetics of vesicular transporters in C. elegans. FASEB J 14: 2414–2422.
- Rex E, Molitor SC, Hapiak V, Xiao H, Henderson M, Komuniecki R. 2004. Tyramine receptor isoforms are involved in the regulation of pharyngeal pumping and foraging behavior in Caenorhabditis elegans. J Neurochem 91: 1104–1115.
- Rogers CM, Franks CJ, Walker RJ, Burke JF, Holden-Dye L. 2001. Regulation of the pharynx of Caenorhabditis elegans by 5-HT, octopamine and FMRFamide-like neuropeptides. J Neurobiol 49: 235–244.
- Rosoff ML, Burglin TR, Li C. 1992. Alternatively spliced transcripts of the flp-1 gene encode distinct FMRFamide-like peptides in Caenorhabditis elegans. J Neurosci 12: 2356–2361.
- Rosoff ML, Doble KE, Price DA, Li C. 1993. The flp-1 propeptide is processed into multiple, highly similar FMRFamide-like peptides in Caenorhabditis elegans. Peptides 14: 331–338.
- Sawin ER, Ranganathan R, Horvitz HR. 2000. C. elegans locomotion rate is modulated by the environment through a dopaminergic pathway and by experience through a serotonergic pathway. Neuron 26: 619–631.
- Shimozono S, Fukano T, Kimura KD, Mori I, Kirino Y, Miyawaki A. 2004. Slow calcium dynamics in pharyngeal muscle in Caenorhabditis elegans during fast pumping. EMBO Rep 5: 521–526.
- Sithigorngul P, Stretton AW, Cowden C. 1990. Neuropeptide diversity in Ascaris—an immunocytochemical study. J Comp Neurol 294: 362–376.
- Sze JY, Victor M, Loer C, Shi Y, Ruvkun G. 2000. Food and metabolic signaling defects in a Caenorhabditis elegans serotonin-synthesis mutant. Nature 403: 560–564.
- Tsalik EL, Niacaris T, Wenick AS, Pau K, Avery L, Hobert O. 2003. LIM homeobox gene-dependent expression of biogenic amine receptors in restricted regions of the C. elegans nervous system. Dev Biol 263: 81–102.
- Waggoner LE, Hardaker L, Golik S, Schafer W. 2000. Effect of a neuropeptide gene on behavioral states in Caenorhabditis elegans egg-laying. Genetics 154: 1181–1192.
- Walker RJ. 1992. Neuroactive peptides with an RFamide or Famide carboxyl terminal. Comp Biochem Physiol 102C: 213–222.
- Weimann JM, Skiebe P, Heinzel HG, Soto C, Kopell N, JorgeRivera JC, Marder E. 1997. Modulation of oscillator interactions in the crab stomatogastric ganglion by crustacean cardioactive peptide. J Neurosci 17: 1748–1760.
- www.wormatlas.org