Hostname: page-component-cd9895bd7-jkksz Total loading time: 0 Render date: 2024-12-24T18:48:23.321Z Has data issue: false hasContentIssue false
  • English
  • Français

A novel member of the ligand-gated chloride channel gene family from Haemonchus contortus

Published online by Cambridge University Press:  20 December 2007

S. G. FORRESTER  and
S. Z. SIDDIQUI
S. G. FORRESTER*
Affiliation:
Faculty of Science, University of Ontario Institute of Technology, 2000 Simcoe Street North Oshawa, ON L1H 7K4, Canada
S. Z. SIDDIQUI
Affiliation:
Faculty of Science, University of Ontario Institute of Technology, 2000 Simcoe Street North Oshawa, ON L1H 7K4, Canada
*
*Corresponding author: Tel: +1 905 721 8668 ext 2937. Fax: +1 905 721 3304. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

Ligand-gated chloride channels (LGCCs) are key components of the nervous system of parasitic nematodes and important targets for anthelmintics. Here, we describe the isolation and characterization of a novel member of the LGCC gene family (HcLGCC1) from the parasitic nematode Haemonchus contortus. Sequence analysis revealed that the channel subunit encoded by HcLGCC1 is anion selective and a member of a group of channels characterized as having two Cys-loops in the N-terminal ligand-binding domain†. Although the overall function of HcLGCC1 is presently unknown, the gene may play a key role in the early developmental stages of the parasite. Further investigations into the function of LGCCs, such as HcLGCC1, in parasitic nematodes should have implications for the discovery of new anthelmintic targets.

Keywords

ligand-gated chloride channelneurotransmitter receptormolecular cloningHaemonchus contortus
Type
Original Articles
Information
Parasitology , Volume 135 , Issue 4 , April 2008 , pp. 539 - 545
Copyright
Copyright © Cambridge University Press 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Bamber, B. A., Beg, A. A., Twyman, R. E. and Jorgensen, E. M. (1999). The Caenorhabditis elegans unc-49 locus encodes multiple subunits of a heteromultimeric GABA receptor. The Journal of Neuroscience 19, 5348–5359.CrossRefGoogle ScholarPubMed
C. elegans Sequencing Consortium (1998). Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282, 2012–2018.CrossRefGoogle Scholar
Cully, D. F., Vassilatis, D. K., Liu, K. K., Paress, P. S., Van der Ploeg, L. H., Schaeffer, J. M. and Arena, J. P. (1994). Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. Nature, London 371, 707–711. doi: 10.1038/371707a0.CrossRefGoogle ScholarPubMed
Delany, N. S., Laughton, D. L. and Wolstenholme, A. J. (1998). Cloning and localisation of an avermectin receptor-related subunit from Haemonchus contortus. Molecular and Biochemical Parasitology 97, 177–187.CrossRefGoogle ScholarPubMed
Dent, J. A. (2006). Evidence for a diverse Cys-loop ligand-gated ion channel superfamily in early bilateria. Journal of Molecular Evolution 62, 523–535. doi: 10.1007/s00239-005-0018-2.CrossRefGoogle ScholarPubMed
Dent, J. A., Davis, M. W. and Avery, L. (1997). avr-15 encodes a chloride channel subunit that mediates inhibitory glutamatergic neurotransmission and ivermectin sensitivity in Caenorhabditis elegans. The EMBO Journal 16, 5867–5879. doi: 10.1093/emboj/16.19.5867.CrossRefGoogle ScholarPubMed
Feng, X. P., Hayashi, J., Beech, R. N. and Prichard, R. K. (2002). Study of the nematode putative GABA type-A receptor subunits: evidence for modulation by ivermectin. Journal of Neurochemistry 83, 870–878.CrossRefGoogle ScholarPubMed
Forrester, S. G., Hamdan, F. F., Prichard, R. K. and Beech, R. N. (1999). Cloning, sequencing, and developmental expression levels of a novel glutamate-gated chloride channel homologue in the parasitic nematode Haemonchus contortus. Biochemical and Biophysical Research Communications 254, 529–534. doi: 10.1006/bbrc.1998.0106.CrossRefGoogle ScholarPubMed
Frohman, M. A., Dush, M. K. and Martin, G. R. (1988). Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proceedings of the National Academy of Sciences, USA 85, 8998–9002.CrossRefGoogle ScholarPubMed
Galzi, J. L., Devillers-Thiery, A., Hussy, N., Bertrand, S., Changeux, J. P. and Bertrand, D. (1992). Mutations in the channel domain of a neuronal nicotinic receptor convert ion selectivity from cationic to anionic. Nature, London 359, 500–505. doi: 10.1038/359500a0.CrossRefGoogle ScholarPubMed
Gisselmann, G., Pusch, H., Hovemann, B. T. and Hatt, H. (2002). Two cDNAs coding for histamine-gated ion channels in D. melanogaster. Nature Neuroscience 5, 11–12. doi: 10.1038/nn787.CrossRefGoogle ScholarPubMed
Horoszok, L., Raymond, V., Sattelle, D. B. and Wolstenholme, A. J. (2001). GLC-3: a novel fipronil and BIDN-sensitive, but picrotoxinin-insensitive, L-glutamate-gated chloride channel subunit from Caenorhabditis elegans. British Journal of Pharmacology 132, 1247–1254. doi: 10.1038/sj.bjp.0703937.CrossRefGoogle ScholarPubMed
Huang, X. Y. and Hirsh, D. (1989). A second trans-spliced RNA leader sequence in the nematode Caenorhabditis elegans. Proceedings of the National Academy of Sciences, USA 86, 8640–8644.CrossRefGoogle ScholarPubMed
Jagannathan, S., Laughton, D. L., Critten, C. L., Skinner, T. M., Horoszok, L. and Wolstenholme, A. J. (1999). Ligand-gated chloride channel subunits encoded by the Haemonchus contortus and Ascaris suum orthologues of the Caenorhabditis elegans gbr-2 (avr-14) gene. Molecular and Biochemical Parasitology 103, 129–140.CrossRefGoogle ScholarPubMed
Laughton, D. L., Amar, M., Thomas, P., Towner, P., Harris, P., Lunt, G. G. and Wolstenholme, A. J. (1994). Cloning of a putative inhibitory amino acid receptor subunit from the parasitic nematode Haemonchus contortus. Receptors and Channels 2, 155–163.Google ScholarPubMed
Nielsen, H., Engelbrecht, J., Brunak, S. and von Heijne, G. (1997). Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Protein Engineering 10, 1–6.CrossRefGoogle ScholarPubMed
Njue, A. I., Hayashi, J., Kinne, L., Feng, X. P. and Prichard, R. K. (2004). Mutations in the extracellular domains of glutamate-gated chloride channel alpha3 and beta subunits from ivermectin-resistant Cooperia oncophora affect agonist sensitivity. Journal of Neurochemistry 89, 1137–1147. doi: 10.1111/j.1471-41592004.02379.x.CrossRefGoogle ScholarPubMed
Ortells, M. O. and Lunt, G. G. (1995). Evolutionary history of the ligand-gated ion-channel superfamily of receptors. Trends in Neurosciences 18, 121–127.CrossRefGoogle ScholarPubMed
Putrenko, I., Zakikhani, M. and Dent, J. A. (2005). A family of acetylcholine-gated chloride channel subunits in Caenorhabditis elegans. The Journal of Biological Chemistry 280, 6392–6398. doi: 10.1074/jbc.M412644200.CrossRefGoogle ScholarPubMed
Rajendra, S., Vandenberg, R. J., Pierce, K. D., Cunningham, A. M., French, P. W., Barry, P. H. and Schofield, P. R. (1995). The unique extracellular disulfide loop of the glycine receptor is a principal ligand binding element. The EMBO Journal 14, 2987–2998.CrossRefGoogle ScholarPubMed
Ranganathan, R., Cannon, S. C. and Horvitz, H. R. (2000). MOD-1 is a serotonin-gated chloride channel that modulates locomotory behaviour in C. elegans. Nature, London 408, 470–475. doi: 10.1038/35044083.CrossRefGoogle ScholarPubMed
Raymond, V. and Sattelle, D. B. (2002). Novel animal-health drug targets from ligand-gated chloride channels. Nature reviews. Drug Discovery 1, 427–436.CrossRefGoogle ScholarPubMed
Schnizler, K., Saeger, B., Pfeffer, C., Gerbaulet, A., Ebbinghaus-Kintscher, U., Methfessel, C., Franken, E. M., Raming, K., Wetzel, C. H., Saras, A., Pusch, H., Hatt, H. and Gisselmann, G. (2005). A novel chloride channel in Drosophila melanogaster is inhibited by protons. The Journal of Biological Chemistry 280, 16254–16262. doi: 10.1074/jbc.M411759200.CrossRefGoogle ScholarPubMed
Tandon, R., LePage, K. T. and Kaplan, R. M. (2006). Cloning and characterization of genes encoding alpha and beta subunits of glutamate-gated chloride channel protein in Cylicocyclus nassatus. Molecular and Biochemical Parasitology 150, 46–55. doi: 10.1016/j.molbiopara.2006.06.007.CrossRefGoogle ScholarPubMed
Tasneem, A., Iyer, L. M., Jakobsson, E. and Aravind, L. (2004). Identification of the prokaryotic ligand-gated ion channels and their implications for the mechanisms and origins of animal Cys-loop ion channels. Genome Biology 6, R4. doi: 10.1186/gb-2004-6-1-r4.CrossRefGoogle ScholarPubMed
Unwin, N. (1993). Neurotransmitter action: opening of ligand-gated ion channels. Cell 72 (Suppl.) 31–41.CrossRefGoogle ScholarPubMed
Weston, D., Patel, B. and Van Voorhis, W. C. (1999). Virulence in Trypanosoma cruzi infection correlates with the expression of a distinct family of sialicase superfamily genes. Molecular and Biochemical Parasitology 98, 105–116. doi: 10.1016/S0166-6851(98)00152-2.CrossRefGoogle ScholarPubMed
Wolstenholme, A. J. and Rogers, A. T. (2005). Glutamate-gated chloride channels and the mode of action of the avermectin/milbemycin anthelmintics. Parasitology 131 (Suppl.) S85–S95. doi: 10.1017/S0031182005008218.CrossRefGoogle ScholarPubMed
Yates, D. M. and Wolstenholme, A. J. (2004 a). Dirofilaria immitis: identification of a novel ligand-gated ion channel-related polypeptide. Experimental Parasitology 108, 182–185. doi: 10.1016/j.exppara.2004.08.003.CrossRefGoogle ScholarPubMed
Yates, D. M. and Wolstenholme, A. J. (2004 b). An ivermectin-sensitive glutamate-gated chloride channel subunit from Dirofilaria immitis. International Journal for Parasitology 34, 1075–1081. doi: 10.1016/j.ijpara.2004.04.010.CrossRefGoogle ScholarPubMed
Zheng, Y., Hirschberg, B., Yuan, J., Wang, A. P., Hunt, D. C., Ludmerer, S. W., Schmatz, D. M. and Cully, D. F. (2002). Identification of two novel Drosophila melanogaster histamine-gated chloride channel subunits expressed in the eye. The Journal of Biological Chemistry 277, 2000–2005. doi: 10.1074/jbc.M107635200.CrossRefGoogle ScholarPubMed