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Gene Review

nlp-13  -  Protein NLP-13

Caenorhabditis elegans

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Disease relevance of neuropeptide

  • Using a systemic and continuous delivery method based on feeding on a particular strain of transformed Escherichia coli to induce double stranded RNA-mediated interference, we targeted the product of the npr-1 gene, a putative Caenorhabditis elegans homologue of a neuropeptide Y receptor, a G-protein coupled receptor [1].

Psychiatry related information on neuropeptide


High impact information on neuropeptide

  • A loss-of-function mutation in the npr-1 gene, which encodes a predicted G protein-coupled receptor similar to neuropeptide Y receptors, causes a solitary strain to take on social behavior [2].
  • We propose that adaptation to serotonin occurs through activation of an Unc-2-dependent calcium influx, which modulates the postsynaptic response to serotonin, perhaps by inhibiting the release of a potentiating neuropeptide [3].
  • Disruption of a neuropeptide gene, flp-1, causes multiple behavioral defects in Caenorhabditis elegans [4].
  • To identify novel peptidergic neurotransmitters, the Caenorhabditis elegans genome was searched for predicted proteins with the structural hallmarks of neuropeptide preproproteins [5].
  • This behavior is modulated by nutritional cues and ambient oxygen levels, and aggregation is inhibited by the npr-1 G protein-coupled neuropeptide receptor gene [6].

Biological context of neuropeptide

  • The results are discussed in relation to the possibility of a hormonal role for ecdysteroids and neuropeptide-like compounds in the control of ecdysis in filarial nematodes, that maybe somewhat comparable to the system which is found in insects [7].
  • With the ongoing EST projects and DNA sequence determination of different genomes, the identification of neuropeptide genes has been made easier [8].
  • Emodepside caused (i) muscle relaxation, (ii) inhibition of muscle contraction elicited by either acetylcholine (ACh), or the neuropeptide, AF2 (KHEYLRFamide) and (iii) a rapid relaxation of muscle tonically contracted by ACh [9].
  • The promoter of the neuropeptide gene expressed in the DD mns contains putative binding sites for both UNC-30 and UNC-55; alteration of these sites suggests that UNC-55 represses the ability of UNC-30 to activate a subset of genes that are expressed in the DD mns but not in the VD mns [10].
  • The profound changes in cAMP produced by some neuropeptides has important implications for understanding cAMP signaling and shows that neuropeptide-mediated signal transduction pathways are potential targets for anthelmintic drug development [11].

Anatomical context of neuropeptide

  • We provide evidence that in a distinct subset of neurones in the ventral, dorsal and lateral ganglia NADPH diaphorase staining and SALMFamide-like immunoreactivity are co-localized, suggesting a possible role for nitric oxide in modulating neuropeptide activity in these regions [12].
  • The action of serotonin and the nematode neuropeptide KSAYMRFamide on the pharyngeal muscle of the parasitic nematode, Ascaris suum [13].
  • Finally, electrophysiological recording of the pharyngeal activity showed a high sensitivity of the nep-1 pharynx to serotonin (5-HT) and to the neuropeptide AF1 (C.elegans FLP-8), indicating that NEP-1 is a central component that controls the neuronal innervation of pharyngeal pumping in C.elegans [14].
  • In C. elegans, IDA-1-expressing cells comprised a subset of those expressing the PC2 homolog KPC-2 (C51E3. 7), consistent with IDA-1 being a component of neuropeptide-containing dense core vesicles [15].
  • This is the first report of the construction of a cell line stably expressing a C. elegans neuropeptide receptor [16].

Associations of neuropeptide with chemical compounds


Physical interactions of neuropeptide

  • This natural variation in behaviour is associated with a single residue difference in NPR-1, a predicted G-protein-coupled neuropeptide receptor related to Neuropeptide Y receptors [21].

Other interactions of neuropeptide


Analytical, diagnostic and therapeutic context of neuropeptide


  1. Altered behaviour following RNA interference knockdown of a C. elegans G-protein coupled receptor by ingested double stranded RNA. Vaz Gomes, A., Wahlestedt, C. Eur. J. Pharmacol. (2000) [Pubmed]
  2. Natural variation in a neuropeptide Y receptor homolog modifies social behavior and food response in C. elegans. de Bono, M., Bargmann, C.I. Cell (1998) [Pubmed]
  3. A calcium-channel homologue required for adaptation to dopamine and serotonin in Caenorhabditis elegans. Schafer, W.R., Kenyon, C.J. Nature (1995) [Pubmed]
  4. Disruption of a neuropeptide gene, flp-1, causes multiple behavioral defects in Caenorhabditis elegans. Nelson, L.S., Rosoff, M.L., Li, C. Science (1998) [Pubmed]
  5. Identification of neuropeptide-like protein gene families in Caenorhabditiselegans and other species. Nathoo, A.N., Moeller, R.A., Westlund, B.A., Hart, A.C. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  6. The Caenorhabditis elegans AHR-1 transcription complex controls expression of soluble guanylate cyclase genes in the URX neurons and regulates aggregation behavior. Qin, H., Zhai, Z., Powell-Coffman, J.A. Dev. Biol. (2006) [Pubmed]
  7. The effect of invertebrate hormones and potential hormone inhibitors on the third larval moult of the filarial nematode, Dirofilaria immitis, in vitro. Warbrick, E.V., Barker, G.C., Rees, H.H., Howells, R.E. Parasitology (1993) [Pubmed]
  8. The ever-expanding neuropeptide gene families in the nematode Caenorhabditis elegans. Li, C. Parasitology (2005) [Pubmed]
  9. The effect of the anthelmintic emodepside at the neuromuscular junction of the parasitic nematode Ascaris suum. Willson, J., Amliwala, K., Harder, A., Holden-Dye, L., Walker, R.J. Parasitology (2003) [Pubmed]
  10. Convergent genetic programs regulate similarities and differences between related motor neuron classes in Caenorhabditis elegans. Shan, G., Kim, K., Li, C., Walthall, W.W. Dev. Biol. (2005) [Pubmed]
  11. Changes in locomotory behavior and cAMP produced in Ascaris suum by neuropeptides from Ascaris suum or Caenorhabditis elegans. Reinitz, C.A., Herfel, H.G., Messinger, L.A., Stretton, A.O. Mol. Biochem. Parasitol. (2000) [Pubmed]
  12. NADPH diaphorase activity in peptidergic neurones of the parasitic nematode, Ascaris suum. Bascal, Z.A., Montgomery, A., Holden-Dye, L., Williams, R.G., Thorndyke, M.C., Walker, R.J. Parasitology (1996) [Pubmed]
  13. The action of serotonin and the nematode neuropeptide KSAYMRFamide on the pharyngeal muscle of the parasitic nematode, Ascaris suum. Brownlee, D.J., Holden-Dye, L., Fairweather, I., Walker, R.J. Parasitology (1995) [Pubmed]
  14. Caenorhabditis elegans neprilysin NEP-1: an effector of locomotion and pharyngeal pumping. Spanier, B., Stürzenbaum, S.R., Holden-Dye, L.M., Baumeister, R. J. Mol. Biol. (2005) [Pubmed]
  15. IDA-1, a Caenorhabditis elegans homolog of the diabetic autoantigens IA-2 and phogrin, is expressed in peptidergic neurons in the worm. Zahn, T.R., Macmorris, M.A., Dong, W., Day, R., Hutton, J.C. J. Comp. Neurol. (2001) [Pubmed]
  16. Molecular characterization of two G protein-coupled receptor splice variants as FLP2 receptors in Caenorhabditis elegans. Mertens, I., Meeusen, T., Janssen, T., Nachman, R., Schoofs, L. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  17. Nitric oxide mediates the inhibitory effects of SDPNFLRFamide, a nematode FMRFamide-related neuropeptide, in Ascaris suum. Bowman, J.W., Winterrowd, C.A., Friedman, A.R., Thompson, D.P., Klein, R.D., Davis, J.P., Maule, A.G., Blair, K.L., Geary, T.G. J. Neurophysiol. (1995) [Pubmed]
  18. The FMRFamide-like neuropeptide AF2 is present in the parasitic nematode Haemonchus contortus. Keating, C.D., Holden-Dye, L., Thorndyke, M.C., Williams, R.G., Mallett, A., Walker, R.J. Parasitology (1995) [Pubmed]
  19. Nematode neuropeptide modulation of the vagina vera of Ascaris suum: in vitro effects of PF1, PF2, PF4, AF3 and AF4. Fellowes, R.A., Maule, A.G., Marks, N.J., Geary, T.G., Thompson, D.P., Halton, D.W. Parasitology (2000) [Pubmed]
  20. Identification and properties of a neuropeptide-degrading endopeptidase (neprilysin) of Ascaris suum muscle. Sajid, M., Isaac, R.E. Parasitology (1995) [Pubmed]
  21. Antagonistic pathways in neurons exposed to body fluid regulate social feeding in Caenorhabditis elegans. Coates, J.C., de Bono, M. Nature (2002) [Pubmed]
  22. afp-1: a gene encoding multiple transcripts of a new class of FMRFamide-like neuropeptides in the nematode Ascaris suum. Edison, A.S., Messinger, L.A., Stretton, A.O. Peptides (1997) [Pubmed]
  23. Exploring the Caenorhabditis elegans and Drosophila melanogaster genomes to understand neuropeptide and peptidase function. Coates, D., Siviter, R., Isaac, R.E. Biochem. Soc. Trans. (2000) [Pubmed]
  24. Functional expression and characterization of the cytoplasmic aminopeptidase P of Caenorhabditis elegans. Laurent, V., Brooks, D.R., Coates, D., Isaac, R.E. Eur. J. Biochem. (2001) [Pubmed]
  25. AF1, a sequenced bioactive neuropeptide isolated from the nematode Ascaris suum. Cowden, C., Stretton, A.O., Davis, R.E. Neuron (1989) [Pubmed]
  26. Reduced expression of neuropeptide genes in a genome-wide screen of a secretion-deficient mouse. Bouwman, J., Spijker, S., Schut, D., Wächtler, B., Ylstra, B., Smit, A.B., Verhage, M. J. Neurochem. (2006) [Pubmed]
  27. Regional content of enteric substance P and vasoactive intestinal peptide during intestinal inflammation in the parasitized ferret. Palmer, J.M., Greenwood, B. Neuropeptides (1993) [Pubmed]
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