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The evolution of pentameric ligand-gated ion-channels and the changing family of anthelmintic drug targets

Published online by Cambridge University Press:  30 October 2014

ROBIN N. BEECH  and
CÉDRIC NEVEU
ROBIN N. BEECH*
Affiliation:
French National Institute for Agricultural Research (INRA), UR1282 Infectiologie Animale et santé Publique, Nouzilly F-37380, France Institute of Parasitology, Macdonald Campus, McGill University, 21,111 Lakeshore Road, Ste Anne de Bellevue, Quebec H9X 3V9, Canada
CÉDRIC NEVEU
Affiliation:
French National Institute for Agricultural Research (INRA), UR1282 Infectiologie Animale et santé Publique, Nouzilly F-37380, France
*
* Corresponding author: French National Institute for Agricultural Research (INRA), Infectiologie Animale et santé Publique, Nouzilly, France. E-mail: [email protected]
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Summary

Pentameric ligand-gated ion-channels rapidly transduce synaptic neurotransmitter signals to an electrical response in post-synaptic neuronal or muscle cells and control the neuromusculature of a majority of multicellular animals. A wide range of pharmaceuticals target these receptors including ethanol, nicotine, anti-depressants and other mood regulating drugs, compounds that control pain and mobility and are targeted by a majority of anthelmintic drugs used to control parasitic infection of humans and livestock. Major advances have been made in recent years to our understanding of the structure, function, activity and the profile of compounds that can activate specific receptors. It is becoming clear that these anthelmintic drug targets are not fixed, but differ in significant details from one nematode species to another. Here we review what is known about the evolution of the pentameric ligand-gated ion-channels, paying particular attention to the nematodes, how we can infer the origins of such receptors and understand the factors that determine how they change both over time and from one species to another. Using this knowledge provides a biological framework in which to understand these important drug targets and avenues to identify new receptors and aid the search for new anthelmintic drugs.

Keywords

pentameric ligand-gated ion-channelsgene duplicationgene lossreceptor compositionneurotransmitteranthelmintic target
Type
Review Article
Information
Parasitology , Volume 142 , Issue 2 , February 2015 , pp. 303 - 317
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Copyright
Copyright © Cambridge University Press 2014 

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References

REFERENCES

Accardi, M. V. and Forrester, S. G. (2011). The Haemonchus contortus UNC-49B subunit possesses the residues required for GABA sensitivity in homomeric and heteromeric channels. Molecular and Biochemical Parasitology 178, 15–22.Google Scholar
Aguinaldo, A. M., Turbeville, J. M., Linford, L. S., Rivera, M. C., Garey, J. R., Raff, R. A. and Lake, J. A. (1997). Evidence for a clade of nematodes, arthropods and other moulting animals. Nature 387, 489–493.CrossRefGoogle ScholarPubMed
Althoff, T., Hibbs, R. E., Banerjee, S. and Gouaux, E. (2014). X-ray structures of GluCl in apo states reveal a gating mechanism of Cys-loop receptors. Nature 512, 333–337.Google Scholar
Auerbach, A. (2010). The gating isomerization of neuromuscular acetylcholine receptors. Journal of Physiology 588, 573–586.CrossRefGoogle ScholarPubMed
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. Journal of Neuroscience: the Official Journal of the Society for Neuroscience 19, 5348–5359.Google Scholar
Baylis, H. A., Matsuda, K., Squire, M. D., Fleming, J. T., Harvey, R. J., Darlison, M. G., Barnard, E. A. and Sattelle, D. B. (1997). ACR-3, a Caenorhabditis elegans nicotinic acetylcholine receptor subunit. Molecular cloning and functional expression. Receptors Channels 5, 149–158.Google Scholar
Beech, R. N., Levitt, N., Cambos, M., Zhou, S. and Forrester, S. G. (2010 a). Association of ion-channel genotype and macrocyclic lactone sensitivity traits in Haemonchus contortus . Molecular and Biochemical Parasitology 171, 74–80.CrossRefGoogle ScholarPubMed
Beech, R. N., Wolstenholme, A. J., Neveu, C. and Dent, J. A. (2010 b). Nematode parasite genes: what's in a name? Trends in Parasitology 26, 334–340.Google Scholar
Beech, R. N., Callanan, M. K., Rao, V. T., Dawe, G. B. and Forrester, S. G. (2013). Characterization of cys-loop receptor genes involved in inhibitory amine neurotransmission in parasitic and free living nematodes. Parasitology International 62, 599–605.Google Scholar
Beg, A. A. and Jorgensen, E. M. (2003). EXP-1 is an excitatory GABA-gated cation channel. Nature Neuroscience 6, 1145–1152.CrossRefGoogle ScholarPubMed
Bennett, H. M., Williamson, S. M., Walsh, T. K., Woods, D. J. and Wolstenholme, A. J. (2012). ACR-26: a novel nicotinic receptor subunit of parasitic nematodes. Molecular and Biochemical Parasitology 183, 151–157.Google Scholar
Berriman, M., Haas, B. J., LoVerde, P. T., Wilson, R. A., Dillon, G. P., Cerqueira, G. C., Mashiyama, S. T., Al-Lazikani, B., Andrade, L. F., Ashton, P. D., Aslett, M. A., Bartholomeu, D. C., Blandin, G., Caffrey, C. R., Coghlan, A., Coulson, R., Day, T. A., Delcher, A., DeMarco, R., Djikeng, A., Eyre, T., Gamble, J. A., Ghedin, E., Gu, Y., Hertz-Fowler, C., Hirai, H., Hirai, Y., Houston, R., Ivens, A., Johnston, D. A., et al. (2009). The genome of the blood fluke Schistosoma mansoni . Nature 460, 352–358.Google Scholar
Bocquet, N., Nury, H., Baaden, M., Le Poupon, C., Changeux, J. P., Delarue, M. and Corringer, P. J. (2009). X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation. Nature 457, 111–114.Google Scholar
Boulin, T., Gielen, M., Richmond, J. E., Williams, D. C., Paoletti, P. and Bessereau, J. L. (2008). Eight genes are required for functional reconstitution of the Caenorhabditis elegans levamisole-sensitive acetylcholine receptor. Proceedings of the National Academy of Sciences of the United States of America 105, 18590–18595.Google Scholar
Boulin, T., Fauvin, A., Charvet, C., Cortet, J., Cabaret, J., Bessereau, J. L. and Neveu, C. (2011). Functional reconstitution of Haemonchus contortus acetylcholine receptors in Xenopus oocytes provides mechanistic insights into levamisole resistance. British Journal of Pharmacology 164, 1421–1432.Google Scholar
Bouzat, C. (2012). New insights into the structural bases of activation of Cys-loop receptors. Journal of Physiology, Paris 106, 23–33.Google Scholar
Bouzat, C., Gumilar, F., Spitzmaul, G., Wang, H. L., Rayes, D., Hansen, S. B., Taylor, P. and Sine, S. M. (2004). Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel. Nature 430, 896–900.Google Scholar
Brejc, K., van Dijk, W. J., Klaassen, R. V., Schuurmans, M., van Der Oost, J., Smit, A. B. and Sixma, T. K. (2001). Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors. Nature 411, 269–276.Google Scholar
Buxton, S. K., Charvet, C. L., Neveu, C., Cabaret, J., Cortet, J., Peineau, N., Abongwa, M., Courtot, E., Robertson, A. P. and Martin, R. J. (2014). Investigation of acetylcholine receptor diversity in a nematode parasite leads to characterization of tribendimidine- and derquantel-sensitive nAChRs. PLoS Pathogenesis 10, e1003870.Google Scholar
Carbone, A. L., Moroni, M., Groot-Kormelink, P. J. and Bermudez, I. (2009). Pentameric concatenated (alpha4)(2)(beta2)(3) and (alpha4)(3)(beta2)(2) nicotinic acetylcholine receptors: subunit arrangement determines functional expression. British Journal of Pharmacology 156, 970–981.Google Scholar
Conant, G. C. and Wolfe, K. H. (2008). Turning a hobby into a job: how duplicated genes find new functions. Nature reviews. Genetics 9, 938–950.Google Scholar
Cooper, E. C. and Jan, L. Y. (1999). Ion channel genes and human neurological disease: recent progress, prospects, and challenges. Proceedings of the National Academy of Sciences of the USA 96, 4759–4766.Google Scholar
Corringer, P. J., Baaden, M., Bocquet, N., Delarue, M., Dufresne, V., Nury, H., Prevost, M. and Van Renterghem, C. (2010). Atomic structure and dynamics of pentameric ligand-gated ion channels: new insight from bacterial homologues. Journal of Physiology 588, 565–572.Google 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 371, 707–711.Google Scholar
Cutter, A. D. (2008). Divergence times in Caenorhabditis and Drosophila inferred from direct estimates of the neutral mutation rate. Molecular Biology and Evolution 25, 778–786.Google Scholar
Dacosta, C. J. and Baenziger, J. E. (2013). Gating of pentameric ligand-gated ion channels: structural insights and ambiguities. Structure 21, 1271–1283.CrossRefGoogle ScholarPubMed
Daugelaite, J., O' Driscoll, A. and Sleator, R. D. (2013). An overview of multiple sequence alignments and cloud computing in bioinformatics. ISRN Biomathematics 2013, 14.Google Scholar
Davis, R. E. and Stretton, A. O. (1989). Passive membrane properties of motorneurons and their role in long-distance signaling in the nematode Ascaris. Journal of Neuroscience: the Official Journal of the Society for Neuroscience 9, 403–414.Google Scholar
Dellisanti, C. D., Yao, Y., Stroud, J. C., Wang, Z. Z. and Chen, L. (2007). Crystal structure of the extracellular domain of nAChR alpha1 bound to alpha-bungarotoxin at 1.94 A resolution. Nature Neuroscience 10, 953–962.Google Scholar
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.Google Scholar
Dent, J. A., Smith, M. M., Vassilatis, D. K. and Avery, L. (2000). The genetics of ivermectin resistance in Caenorhabditis elegans . Proceedings of the National Academy of Sciences of the United States of America 97, 2674–2679.Google Scholar
Dermauw, W., Ilias, A., Riga, M., Tsagkarakou, A., Grbic, M., Tirry, L., Van Leeuwen, T. and Vontas, J. (2012). The cys-loop ligand-gated ion channel gene family of Tetranychus urticae: implications for acaricide toxicology and a novel mutation associated with abamectin resistance. Insect Biochemistry and Molecular Biology 42, 455–465.Google Scholar
Desjardins, C. A., Cerqueira, G. C., Goldberg, J. M., Dunning Hotopp, J. C., Haas, B. J., Zucker, J., Ribeiro, J. M., Saif, S., Levin, J. Z., Fan, L., Zeng, Q., Russ, C., Wortman, J. R., Fink, D. L., Birren, B. W. and Nutman, T. B. (2013). Genomics of Loa loa, a Wolbachia-free filarial parasite of humans. Nature Genetics 45, 495–500.Google Scholar
Dunn, C. W., Hejnol, A., Matus, D. Q., Pang, K., Browne, W. E., Smith, S. A., Seaver, E., Rouse, G. W., Obst, M., Edgecombe, G. D., Sorensen, M. V., Haddock, S. H., Schmidt-Rhaesa, A., Okusu, A., Kristensen, R. M., Wheeler, W. C., Martindale, M. Q. and Giribet, G. (2008). Broad phylogenomic sampling improves resolution of the animal tree of life. Nature 452, 745–749.Google Scholar
Engel, M. S. and Grimaldi, D. A. (2004). New light shed on the oldest insect. Nature 427, 627–630.Google Scholar
Epe, C. and Kaminsky, R. (2013). New advancement in anthelmintic drugs in veterinary medicine. Trends Parasitology 29, 129–134.Google Scholar
Felsenstein, J. (1989). PHYLIP – phylogeny inference package (Version 3.2). Cladistics 5, 164–166.Google Scholar
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.Google Scholar
Forrester, S. G., Prichard, R. K., Dent, J. A. and Beech, R. N. (2003). Haemonchus contortus: HcGluCla expressed in Xenopus oocytes forms a glutamate-gated ion channel that is activated by ibotenate and the antiparasitic drug ivermectin. Molecular and Biochemical Parasitology 129, 115–121.CrossRefGoogle ScholarPubMed
Gally, C., Eimer, S., Richmond, J. E. and Bessereau, J. L. (2004). A transmembrane protein required for acetylcholine receptor clustering in Caenorhabditis elegans . Nature 431, 578–582.Google Scholar
Gascuel, O. (1997). BIONJ: an improved version of the NJ algorithm based on a simple model of sequence data. Molecular Biology and Evolution 14, 685–695.Google Scholar
Ghedin, E., Wang, S., Spiro, D., Caler, E., Zhao, Q., Crabtree, J., Allen, J. E., Delcher, A. L., Guiliano, D. B., Miranda-Saavedra, D., Angiuoli, S. V., Creasy, T., Amedeo, P., Haas, B., El-Sayed, N. M., Wortman, J. R., Feldblyum, T., Tallon, L., Schatz, M., Shumway, M., Koo, H., Salzberg, S. L., Schobel, S., Pertea, M., Pop, M., White, O., Barton, G. J., Carlow, C. K., Crawford, M. J., Daub, J., et al. . (2007). Draft genome of the filarial nematode parasite Brugia malayi . Science 317, 1756–1760.Google Scholar
Ghosh, R., Andersen, E. C., Shapiro, J. A., Gerke, J. P. and Kruglyak, L. (2012). Natural variation in a chloride channel subunit confers avermectin resistance in C. elegans . Science 335, 574–578.CrossRefGoogle Scholar
Glendinning, S. K., Buckingham, S. D., Sattelle, D. B., Wonnacott, S. and Wolstenholme, A. J. (2011). Glutamate-gated chloride channels of Haemonchus contortus restore drug sensitivity to ivermectin resistant Caenorhabditis elegans . PLoS ONE 6, e22390.Google Scholar
Goodman, M. B., Hall, D. H., Avery, L. and Lockery, S. R. (1998). Active currents regulate sensitivity and dynamic range in C. elegans neurons. Neuron 20, 763–772.Google Scholar
Grosman, C., Zhou, M. and Auerbach, A. (2000). Mapping the conformational wave of acetylcholine receptor channel gating. Nature 403, 773–776.CrossRefGoogle ScholarPubMed
Guindon, S. and Gascuel, O. (2003). A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Systematic Biology 52, 696–704.CrossRefGoogle ScholarPubMed
Hernando, G., Berge, I., Rayes, D. and Bouzat, C. (2012). Contribution of subunits to Caenorhabditis elegans levamisole-sensitive nicotinic receptor function. Molecular Pharmacology 82, 550–560.Google Scholar
Hibbs, R. E. and Gouaux, E. (2011). Principles of activation and permeation in an anion-selective Cys-loop receptor. Nature 474, 54–60.Google Scholar
Hilf, R. J. and Dutzler, R. (2008). X-ray structure of a prokaryotic pentameric ligand-gated ion channel. Nature 452, 375–379.Google Scholar
Hilf, R. J. and Dutzler, R. (2009). Structure of a potentially open state of a proton-activated pentameric ligand-gated ion channel. Nature 457, 115–118.Google Scholar
Huelsenbeck, J. P. and Ronquist, F. (2001). MRBAYES: bayesian inference of phylogenetic trees. Bioinformatics 17, 754–755.Google Scholar
Hughes, A. L. (1994). Evolution of cysteine proteinases in eukaryotes. Molecular Phylogenetics and Evolution 3, 310–321.Google Scholar
Hughes, A. L. and Nei, M. (1988). Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature 335, 167–170.Google Scholar
Jones, A. K. and Sattelle, D. B. (2006). The cys-loop ligand-gated ion channel superfamily of the honeybee, Apis mellifera . Invertebrate Neuroscience: IN 6, 123–132.Google Scholar
Jones, A. K. and Sattelle, D. B. (2007). The cys-loop ligand-gated ion channel gene superfamily of the red flour beetle, Tribolium castaneum. BMC Genomics 8, 327.Google Scholar
Jones, A. K. and Sattelle, D. B. (2008). The cys-loop ligand-gated ion channel gene superfamily of the nematode, Caenorhabditis elegans . Invertebrate Neuroscience: IN 8, 41–47.CrossRefGoogle ScholarPubMed
Jones, A. K. and Sattelle, D. B. (2010). Diversity of insect nicotinic acetylcholine receptor subunits. Advances in Experimental Medicine and Biology 683, 25–43.Google Scholar
Jones, A. K., Elgar, G. and Sattelle, D. B. (2003). The nicotinic acetylcholine receptor gene family of the pufferfish, Fugu rubripes. Genomics 82, 441–451.Google Scholar
Jones, A. K., Raymond-Delpech, V., Thany, S. H., Gauthier, M. and Sattelle, D. B. (2006). The nicotinic acetylcholine receptor gene family of the honey bee, Apis mellifera. Genome Research 16, 1422–1430.Google Scholar
Jones, A. K., Davis, P., Hodgkin, J. and Sattelle, D. B. (2007). The nicotinic acetylcholine receptor gene family of the nematode Caenorhabditis elegans: an update on nomenclature. Invertebrate Neuroscience: IN 7, 129–131.Google Scholar
Jones, A. K., Bera, A. N., Lees, K. and Sattelle, D. B. (2010). The cys-loop ligand-gated ion channel gene superfamily of the parasitoid wasp, Nasonia vitripennis . Heredity (Edinb) 104, 247–259.Google Scholar
Jospin, M., Qi, Y. B., Stawicki, T. M., Boulin, T., Schuske, K. R., Horvitz, H. R., Bessereau, J. L., Jorgensen, E. M. and Jin, Y. (2009). A neuronal acetylcholine receptor regulates the balance of muscle excitation and inhibition in Caenorhabditis elegans . PLoS Biology 7, e1000265.CrossRefGoogle ScholarPubMed
Kaminsky, R., Ducray, P., Jung, M., Clover, R., Rufener, L., Bouvier, J., Weber, S. S., Wenger, A., Wieland-Berghausen, S., Goebel, T., Gauvry, N., Pautrat, F., Skripsky, T., Froelich, O., Komoin-Oka, C., Westlund, B., Sluder, A. and Maser, P. (2008). A new class of anthelmintics effective against drug-resistant nematodes. Nature 452, 176–180.Google Scholar
Katoh, K., Misawa, K., Kuma, K. and Miyata, T. (2002). MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform. Nucleic Acids Research 30, 3059–3066.Google Scholar
Kesters, D., Thompson, A. J., Brams, M., van Elk, R., Spurny, R., Geitmann, M., Villalgordo, J. M., Guskov, A., Danielson, U. H., Lummis, S. C., Smit, A. B. and Ulens, C. (2013). Structural basis of ligand recognition in 5-HT3 receptors. EMBO Reports 14, 49–56.Google Scholar
Kimura, M. (1968). Evolutionary rate at the molecular level. Nature 217, 624–626.Google Scholar
King, J. L. and Jukes, T. H. (1969). Non-Darwinian evolution. Science 164, 788–798.Google Scholar
Knipple, D. and Soderlund, D. (2012). The ligand-gated chloride channel gene family of Drosophila melanogaster . Pesticide Biochemistry and Physiology 97, 140–148.Google Scholar
Laing, R., Hunt, M., Protasio, A. V., Saunders, G., Mungall, K., Laing, S., Jackson, F., Quail, M., Beech, R., Berriman, M. and Gilleard, J. S. (2011). Annotation of two large contiguous regions from the Haemonchus contortus genome using RNA-seq and comparative analysis with Caenorhabditis elegans . PLoS ONE 6, e23216.Google Scholar
Laing, R., Kikuchi, T., Martinelli, A., Tsai, I. J., Beech, R. N., Redman, E., Holroyd, N., Bartley, D. J., Beasley, H., Britton, C., Curran, D., Devaney, E., Gilabert, A., Hunt, M., Jackson, F., Johnston, S., Kryukov, I., Li, K., Morrison, A. A., Reid, A. J., Sargison, N., Saunders, G., Wasmuth, J. D., Wolstenholme, A., Berriman, M., Gilleard, J. S. and Cotton, J. A. (2013). The genome and transcriptome of Haemonchus contortus, a key model parasite for drug and vaccine discovery. Genome Biology 14, R88.Google Scholar
Lane, N. (2010). Chance or necessity? bioenergetics and the probability of life. Journal of Cosmology 20, 3286–3304.Google Scholar
Lee, J., Song, H. O., Jee, C., Vanoaica, L. and Ahnn, J. (2005). Calcineurin regulates enteric muscle contraction through EXP-1, excitatory GABA-gated channel, in C. elegans . Journal of Molecular Biology 352, 313–318.CrossRefGoogle ScholarPubMed
Lee, W. Y. and Sine, S. M. (2005). Principal pathway coupling agonist binding to channel gating in nicotinic receptors. Nature 438, 243–247.Google Scholar
Le Novere, N. and Changeux, J. P. (1995). Molecular evolution of the nicotinic acetylcholine receptor: an example of multigene family in excitable cells. Journal of Molecular Evolution 40, 155–172.Google Scholar
Lewis, J. A., Wu, C. H., Berg, H. and Levine, J. H. (1980 a). The genetics of levamisole resistance in the nematode Caenorhabditis elegans . Genetics 95, 905–928.Google Scholar
Lewis, J. A., Wu, C. H., Levine, J. H. and Berg, H. (1980 b). Levamisole-resistant mutants of the nematode Caenorhabditis elegans appear to lack pharmacological acetylcholine receptors. Neuroscience 5, 967–989.Google Scholar
Li, W. H., Wu, C. I. and Luo, C. C. (1985). A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes. Molecular Biology and Evolution 2, 150–174.Google Scholar
Liu, Y., Han, N., Franchini, L. F., Xu, H., Pisciottano, F., Elgoyhen, A. B., Rajan, K. E. and Zhang, S. (2012). The voltage-gated potassium channel subfamily KQT member 4 (KCNQ4) displays parallel evolution in echolocating bats. Molecular Biology and Evolution 29, 1441–1450.Google Scholar
Lynagh, T., Beech, R. N., Lalande, M. J., Keller, K., Cromer, B. A., Wolstenholme, A. J. and Laube, B. (2014). Molecular basis for convergent evolution of glutamate recognition by pentameric ligand-gated ion-channels. Scientific Reports. Submitted.Google Scholar
Lynch, M. and Conery, J. S. (2003). The origins of genome complexity. Science 302, 1401–1404.Google Scholar
Ma, Z., Huang, J., Sun, J., Wang, G., Li, C., Xie, L. and Zhang, R. (2007). A novel extrapallial fluid protein controls the morphology of nacre lamellae in the pearl oyster, Pinctada fucata . Journal of Biological Chemistry 282, 23253–23263.Google Scholar
Magis, C., Taly, J. F., Bussotti, G., Chang, J. M., Di Tommaso, P., Erb, I., Espinosa-Carrasco, J. and Notredame, C. (2014). T-Coffee: tree-based consistency objective function for alignment evaluation. Methods in Molecular Biology 1079, 117–129.Google Scholar
Martin, R. J. and Robertson, A. P. (2010). Control of nematode parasites with agents acting on neuro-musculature systems: lessons for neuropeptide ligand discovery. Advances in Experimental Medicine and Biology 692, 138–154.Google Scholar
Meldal, B. H., Debenham, N. J., De Ley, P., De Ley, I. T., Vanfleteren, J. R., Vierstraete, A. R., Bert, W., Borgonie, G., Moens, T., Tyler, P. A., Austen, M. C., Blaxter, M. L., Rogers, A. D. and Lambshead, P. J. (2007). An improved molecular phylogeny of the Nematoda with special emphasis on marine taxa. Molecular Phylogenetics and Evolution 42, 622–636.Google Scholar
Mellem, J. E., Brockie, P. J., Madsen, D. M. and Maricq, A. V. (2008). Action potentials contribute to neuronal signaling in C. elegans . Nature Neuroscience 11, 865–867.CrossRefGoogle ScholarPubMed
Miller, P. S. and Aricescu, A. R. (2014). Crystal structure of a human GABA receptor. Nature 512, 270–275.Google Scholar
Miyata, T., Yasunaga, T., Yamawaki-Kataoka, Y., Obata, M. and Honjo, T. (1980). Nucleotide sequence divergence of mouse immunoglobulin gamma 1 and gamma 2b chain genes and the hypothesis of intervening sequence-mediated domain transfer. Proceedings of the National Academy of Sciences of the United States of America 77, 2143–2147.Google Scholar
Mowrey, D., Chen, Q., Liang, Y., Liang, J., Xu, Y. and Tang, P. (2013 a). Signal transduction pathways in the pentameric ligand-gated ion channels. PLoS ONE 8, e64326.Google Scholar
Mowrey, D., Cheng, M. H., Liu, L. T., Willenbring, D., Lu, X., Wymore, T., Xu, Y. and Tang, P. (2013 b). Asymmetric ligand binding facilitates conformational transitions in pentameric ligand-gated ion channels. Journal of the American Chemical Society 135, 2172–2180.Google Scholar
Mu, T. W., Lester, H. A. and Dougherty, D. A. (2003). Different binding orientations for the same agonist at homologous receptors: a lock and key or a simple wedge? Journal of the American Chemical Society 125, 6850–6851.Google Scholar
Nei, M. and Gojobori, T. (1986). Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Molecular Biology and Evolution 3, 418–426.Google ScholarPubMed
Neveu, C., Charvet, C. L., Fauvin, A., Cortet, J., Beech, R. N. and Cabaret, J. (2010). Genetic diversity of levamisole receptor subunits in parasitic nematode species and abbreviated transcripts associated with resistance. Pharmacogenetics and Genomics 20, 414–425.Google Scholar
Ohno, S. (1970). Evolution by Gene Duplication Berlin. Springer-Verlag, New York.Google Scholar
Ortells, M. O. and Lunt, G. G. (1995). Evolutionary history of the ligand-gated ion-channel superfamily of receptors. Trends in Neuroscience 18, 121–127.Google Scholar
Patthy, L. (2008). Protein Evolution. Blackwell Publishing, Oxford, UK.Google Scholar
Putrenko, I., Zakikhani, M. and Dent, J. A. (2005). A family of acetylcholine-gated chloride channel subunits in Caenorhabditis elegans . Journal of Biological Chemistry 280, 6392–6398.Google Scholar
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 408, 470–475.Google Scholar
Rao, V. T., Siddiqui, S. Z., Prichard, R. K. and Forrester, S. G. (2009). A dopamine-gated ion channel (HcGGR3*) from Haemonchus contortus is expressed in the cervical papillae and is associated with macrocyclic lactone resistance. Molecular and Biochemical Parasitology 166, 54–61.Google Scholar
Rao, V. T., Accardi, M. V., Siddiqui, S. Z., Beech, R. N., Prichard, R. K. and Forrester, S. G. (2010). Characterization of a novel tyramine-gated chloride channel from Haemonchus contortus . Molecular and Biochemical Parasitology 173, 64–68.Google Scholar
Rendon, G., Kantorovitz, M. R., Tilson, J. L. and Jakobsson, E. (2011). Identifying bacterial and archaeal homologs of pentameric ligand-gated ion channel (pLGIC) family using domain-based and alignment-based approaches. Channels (Austin) 5, 325–343.Google Scholar
Rufener, L., Maser, P., Roditi, I. and Kaminsky, R. (2009). Haemonchus contortus acetylcholine receptors of the DEG-3 subfamily and their role in sensitivity to monepantel. PLoS Pathogens 5, e1000380.CrossRefGoogle ScholarPubMed
Rufener, L., Baur, R., Kaminsky, R., Maser, P. and Sigel, E. (2010 a). Monepantel allosterically activates DEG-3/DES-2 channels of the gastrointestinal nematode Haemonchus contortus . Molecular Pharmacology 78, 895–902.Google Scholar
Rufener, L., Keiser, J., Kaminsky, R., Maser, P. and Nilsson, D. (2010 b). Phylogenomics of ligand-gated ion channels predicts monepantel effect. PLoS pathogens 6, e1001091.Google Scholar
Rufener, L., Bedoni, N., Baur, R., Rey, S., Glauser, D. A., Bouvier, J., Beech, R., Sigel, E. and Puoti, A. (2013). Acr-23 encodes a monepantel-sensitive channel in caenorhabditis elegans . PLoS Pathogens 9, e1003524.Google Scholar
Schwarz, E. M., Korhonen, P. K., Campbell, B. E., Young, N. D., Jex, A. R., Jabbar, A., Hall, R. S., Mondal, A., Howe, A. C., Pell, J., Hofmann, A., Boag, P. R., Zhu, X. Q., Gregory, T. R., Loukas, A., Williams, B. A., Antoshechkin, I., Brown, C. T., Sternberg, P. W. and Gasser, R. B. (2013). The genome and developmental transcriptome of the strongylid nematode Haemonchus contortus . Genome Biology 14, R89.Google Scholar
Shao, Y. M., Dong, K. and Zhang, C. X. (2007). The nicotinic acetylcholine receptor gene family of the silkworm, Bombyx mori. BMC Genomics 8, 324.Google Scholar
Siddiqui, S. Z., Brown, D. D., Rao, V. T. and Forrester, S. G. (2010). An UNC-49 GABA receptor subunit from the parasitic nematode Haemonchus contortus is associated with enhanced GABA sensitivity in nematode heteromeric channels. Journal of Neurochemistry 113, 1113–1122.Google Scholar
Sievers, F. and Higgins, D. G. (2014). Clustal Omega, accurate alignment of very large numbers of sequences. Methods in Molecular Biology 1079, 105–116.Google Scholar
Sine, S. M. (2002). The nicotinic receptor ligand binding domain. Journal of Neurobiology 53, 431–446.Google Scholar
Smart, T. G. and Paoletti, P. (2012). Synaptic neurotransmitter-gated receptors. Cold Spring Harbour Perspectives in Biology 4, a009662.Google Scholar
Smit, A. B., Syed, N. I., Schaap, D., van Minnen, J., Klumperman, J., Kits, K. S., Lodder, H., van der Schors, R. C., van Elk, R., Sorgedrager, B., Brejc, K., Sixma, T. K. and Geraerts, W. P. (2001). A glia-derived acetylcholine-binding protein that modulates synaptic transmission. Nature 411, 261–268.Google Scholar
Swanson, K. W., Irwin, D. M. and Wilson, A. C. (1991). Stomach lysozyme gene of the langur monkey: tests for convergence and positive selection. Journal of Molecular Evolution 33, 418–425.Google Scholar
Tasneem, A., Iyer, L. M., Jakobsson, E. and Aravind, L. (2005). 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.Google Scholar
Touroutine, D., Fox, R. M., Von Stetina, S. E., Burdina, A., Miller, D. M. III and Richmond, J. E. (2005). acr-16 encodes an essential subunit of the levamisole-resistant nicotinic receptor at the Caenorhabditis elegans neuromuscular junction. Journal of Biological Chemistry 280, 27013–27021.Google Scholar
Treinin, M., Gillo, B., Liebman, L. and Chalfie, M. (1998). Two functionally dependent acetylcholine subunits are encoded in a single Caenorhabditis elegans operon. Proceedings of the National Academy of Sciences of the USA 95, 15492–15495.CrossRefGoogle Scholar
Tsai, I. J., Zarowiecki, M., Holroyd, N., Garciarrubio, A., Sanchez-Flores, A., Brooks, K. L., Tracey, A., Bobes, R. J., Fragoso, G., Sciutto, E., Aslett, M., Beasley, H., Bennett, H. M., Cai, J., Camicia, F., Clark, R., Cucher, M., De Silva, N., Day, T. A., Deplazes, P., Estrada, K., Fernandez, C., Holland, P. W., Hou, J., Hu, S., Huckvale, T., Hung, S. S., Kamenetzky, L., Keane, J. A., Kiss, F., et al. (2013). The genomes of four tapeworm species reveal adaptations to parasitism. Nature 496, 57–63.Google Scholar
Unwin, N. (1993). Nicotinic acetylcholine receptor at 9A resolution. Journal of Molecular Biology 229, 1101–1124.Google Scholar
Unwin, N. (1995). Acetylcholine receptor channel imaged in the open state. Nature 373, 37–43.Google Scholar
Unwin, N. (2005). Refined structure of the nicotinic acetylcholine receptor at 4A resolution. Journal of Molecular Biology 346, 967–989.Google Scholar
Unwin, N. and Fujiyoshi, Y. (2012). Gating movement of acetylcholine receptor caught by plunge-freezing. Journal of Molecular Biology 422, 617–634.Google Scholar
Unwin, N., Miyazawa, A., Li, J. and Fujiyoshi, Y. (2002). Activation of the nicotinic acetylcholine receptor involves a switch in conformation of the alpha subunits. Journal of Molecular Biology 319, 1165–1176.Google Scholar
Vallender, E. J. and Lahn, B. T. (2004). Positive selection on the human genome. Human Molecular Genetics 13 Spec No 2, R245–R254.Google Scholar
Williamson, S. M., Walsh, T. K. and Wolstenholme, A. J. (2007). The cys-loop ligand-gated ion channel gene family of Brugia malayi and Trichinella spiralis: a comparison with Caenorhabditis elegans . Invertebrate Neuroscience: IN 7, 219–226.Google Scholar
Williamson, S. M., Robertson, A. P., Brown, L., Williams, T., Woods, D. J., Martin, R. J., Sattelle, D. B. and Wolstenholme, A. J. (2009). The nicotinic acetylcholine receptors of the parasitic nematode Ascaris suum: formation of two distinct drug targets by varying the relative expression levels of two subunits. PLoS Pathogens 5, e1000517.Google Scholar
Xue, H. (1998). Identification of major phylogenetic branches of inhibitory ligand-gated channel receptors. Journal of Molecular Evolution 47, 323–333.Google Scholar
Yassin, L., Gillo, B., Kahan, T., Halevi, S., Eshel, M. and Treinin, M. (2001). Characterization of the deg-3/des-2 receptor: a nicotinic acetylcholine receptor that mutates to cause neuronal degeneration. Molecular and Cellular Neurosciences 17, 589–599.Google Scholar
Yook, K., Harris, T. W., Bieri, T., Cabunoc, A., Chan, J., Chen, W. J., Davis, P., de la Cruz, N., Duong, A., Fang, R., Ganesan, U., Grove, C., Howe, K., Kadam, S., Kishore, R., Lee, R., Li, Y., Muller, H. M., Nakamura, C., Nash, B., Ozersky, P., Paulini, M., Raciti, D., Rangarajan, A., Schindelman, G., Shi, X., Schwarz, E. M., Ann Tuli, M., Van Auken, K., Wang, D., et al. (2012). WormBase 2012: more genomes, more data, new website. Nucleic Acids Research 40, D735–D741.Google Scholar
Zhao, H., Ru, B., Teeling, E. C., Faulkes, C. G., Zhang, S. and Rossiter, S. J. (2009). Rhodopsin molecular evolution in mammals inhabiting low light environments. PLoS ONE 4, e8326.Google Scholar
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. Journal of Biological Chemistry 277, 2000–2005.Google Scholar