Hostname: page-component-7479d7b7d-qlrfm Total loading time: 0 Render date: 2024-07-15T12:42:17.210Z Has data issue: false hasContentIssue false
  • English
  • Français

ShAR2β, a divergent nicotinic acetylcholine receptor subunit from the blood fluke Schistosoma

Published online by Cambridge University Press:  11 January 2007

G. N. BENTLEY ,
A. K. JONES  and
A. AGNEW
G. N. BENTLEY
Affiliation:
The School of Biology, University of Leeds, West Yorkshire, Leeds, LS2 9JT, UK
A. K. JONES*
Affiliation:
MRC Functional Genetics Unit, Department of Physiology, Anatomy and Genetics, Le Gros Clark Building, University of Oxford, South Parks Road, Oxford OX1 3QX, UK
A. AGNEW
Affiliation:
The School of Biology, University of Leeds, West Yorkshire, Leeds, LS2 9JT, UK
*
*Corresponding author: MRC Functional Genetics Unit, Department of Physiology, Anatomy and Genetics, Le Gros Clark Building, University of Oxford, South Parks Road, Oxford OX1 3QX, UK. Tel: +44 1865 272196. Fax: +44 1865 282651. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that mediate the fast actions of the neurotransmitter, acetylcholine. Invertebrate nAChRs are of interest as they are targets of widely-selling insecticides and drugs that control nematode parasites. Here, we report the cloning of ShAR2β, a candidate nAChR subunit from the blood fluke, Schistosoma haematobium, which is the third trematode nAChR subunit to be characterized. While ShAR2β possesses key structural features common to all nAChRs, its amino acid sequence shares considerably low identity with those of insect, nematode and vertebrate nAChR subunits. In particular, the second transmembrane domain of ShAR2β, which lines the ion channel, bears unusual amino acid residues which will likely give rise to a receptor with distinct functional properties. Phylogenetic analysis shows that ShAR2β is a divergent nAChR subunit that may define a clade of trematode-specific subunits. We discuss our findings in the context of potentially exploiting this receptor as a target for controlling schistosome parasites.

Keywords

Schistosomanicotinic acetylcholine receptorcholinergicion channeldegenerate PCR
Type
Research Article
Information
Parasitology , Volume 134 , Issue 6 , June 2007 , pp. 833 - 840
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

Benner, S. A., Cohen, M. A. and Gonnet, G. H. (1994). Amino acid substitution during functionally constrained divergent evolution of protein sequences. Protein Engineering 7, 1323–1332.CrossRefGoogle ScholarPubMed
Bentley, G. N., Jones, A. K. and Agnew, A. (2003). Mapping and sequencing of acetylcholinesterase genes from the platyhelminth blood fluke Schistosoma. Gene 314, 103–112.CrossRefGoogle ScholarPubMed
Bentley, G. N., Jones, A. K. and Agnew, A. (2005). Expression and comparative functional characterisation of recombinant acetylcholinesterase from three species of Schistosoma. Molecular and Biochemical Parasitology 141, 119–123.CrossRefGoogle ScholarPubMed
Bentley, G. N., Jones, A. K., Oliveros Parra, W. G. and Agnew, A. (2004). ShAR1alpha and ShAR1beta: novel putative nicotinic acetylcholine receptor subunits from the platyhelminth blood fluke Schistosoma. Gene 329, 27–38.CrossRefGoogle ScholarPubMed
Bertrand, D., Galzi, J. L., Devillers-Thiery, A., Bertrand, S. and Changeux, J. P. (1993). Mutations at two distinct sites within the channel domain M2 alter calcium permeability of neuronal alpha 7 nicotinic receptor. Proceedings of the National Academy of Sciences, USA 90, 6971–6975.CrossRefGoogle ScholarPubMed
Brown, L. A., Jones, A. K., Buckingham, S. D., Mee, C. J. and Sattelle, D. B. (2006). Contributions from Caenorhabditis elegans functional genetics to antiparasitic drug target identification and validation: nicotinic acetylcholine receptors, a case study. International Journal for Parasitology 36, 617–624.CrossRefGoogle ScholarPubMed
Camacho, M. and Agnew, A. (1995). Glucose uptake rates by Schistosoma mansoni, S. haematobium, and S. bovis adults using a flow in vitro culture system. The Journal of Parasitology 81, 637–640.CrossRefGoogle ScholarPubMed
Camacho, M., Alsford, S. and Agnew, A. (1996). Molecular forms of tegumental and muscle acetylcholinesterases of Schistosoma. Parasitology 112, 199–204.CrossRefGoogle ScholarPubMed
Camacho, M., Alsford, S., Jones, A. and Agnew, A. (1995). Nicotinic acetylcholine receptors on the surface of the blood fluke Schistosoma. Molecular and Biochemical Parasitology 71, 127–134.CrossRefGoogle ScholarPubMed
Camacho, M., Tarrab-Hazdai, R., Espinoza, B., Arnon, R. and Agnew, A. (1994). The amount of acetylcholinesterase on the parasite surface reflects the differential sensitivity of schistosome species to metrifonate. Parasitology 108, 153–160.CrossRefGoogle ScholarPubMed
Corringer, P. J., Le Novere, N. and Changeux, J. P. (2000). Nicotinic receptors at the amino acid level. Annual Review of Pharmacology and Toxicology 40, 431–458.CrossRefGoogle ScholarPubMed
Dyrlov Bendtsen, J., Nielsen, H., Von Heijne, G. and Brunak, S. (2004). Improved prediction of signal peptides: SignalP 3.0. Journal of Molecular Biology 340, 783–795.CrossRefGoogle Scholar
Felsenstein, J. (1985). Confidence limits on phylogenies: an approach using the bootstrap. Evolution 39, 783–791.CrossRefGoogle ScholarPubMed
Hulo, N., Bairoch, A., Bulliard, V., Cerutti, L., De Castro, E., Langendijk-Genevaux, P. S., Pagni, M. and Sigrist, C. J. (2006). The PROSITE database. Nucleic Acids Research 34, D227–230.CrossRefGoogle ScholarPubMed
Imoto, K., Busch, C., Sakmann, B., Mishina, M., Konno, T., Nakai, J., Bujo, H., Mori, Y., Fukuda, K. and Numa, S. (1988). Rings of negatively charged amino acids determine the acetylcholine receptor channel conductance. Nature, London 335, 645–648.CrossRefGoogle ScholarPubMed
Jones, A. K., Bentley, G. N., Oliveros Parra, W. G. and Agnew, A. (2002). Molecular characterization of an acetylcholinesterase implicated in the regulation of glucose scavenging by the parasite Schistosoma. The FASEB Journal 16, 441–443.CrossRefGoogle ScholarPubMed
Jones, A. K., Grauso, M. and Sattelle, D. B. (2005). The nicotinic acetylcholine receptor gene family of the malaria mosquito, Anopheles gambiae. Genomics 85, 176–187.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Jones, A. K. and Sattelle, D. B. (2004). Functional genomics of the nicotinic acetylcholine receptor gene family of the nematode, Caenorhabditis elegans. Bioessays 26, 39–49.CrossRefGoogle ScholarPubMed
Kohler, P. (2001). The biochemical basis of anthelmintic action and resistance. International Journal for Parasitology 31, 336–345.CrossRefGoogle ScholarPubMed
Lansdell, S. J. and Millar, N. S. (2002). Dbeta3, an atypical nicotinic acetylcholine receptor subunit from Drosophila: molecular cloning, heterologous expression and coassembly. Journal of Neurochemistry 80, 1009–1018.CrossRefGoogle ScholarPubMed
Millar, N. S. (2003). Assembly and subunit diversity of nicotinic acetylcholine receptors. Biochemical Society Transactions 31, 869–874.CrossRefGoogle ScholarPubMed
Nishizaki, T. (2003). N-glycosylation sites on the nicotinic ACh receptor subunits regulate receptor channel desensitization and conductance. Brain Research. Molecular Brain Research 114, 172–176.CrossRefGoogle ScholarPubMed
Page, R. D. (1996). TreeView: an application to display phylogenetic trees on personal computers. Computer Applications in the Biosciences: CABIOS 12, 357–358.Google ScholarPubMed
Pancera, C. F., Alves, A. L., Paschoalotti, M. A. and Chieffi, P. P. (1997). Effect of wide spectrum anti-helminthic drugs upon Schistosoma mansoni experimentally infected mice. Revista do Instituto de Medicina Tropical de São Paulo 39, 159–163.CrossRefGoogle ScholarPubMed
Raymond-Delpech, V., Matsuda, K., Sattelle, B. M., Rauh, J. J. and Sattelle, D. B. (2005). Ion channels: molecular targets of neuroactive insecticides. Invertebrate Neuroscience 5, 119–133.CrossRefGoogle ScholarPubMed
Ribeiro-Dos-Santos, G., Verjovski-Almeida, S. and Leite, L. C. (2006). Schistosomiasis-a century searching for chemotherapeutic drugs. Parasitology Research 99, 505–521.CrossRefGoogle ScholarPubMed
Ribeiro, P., El-Shehabi, F. and Patocka, N. (2005). Classical transmitters and their receptors in flatworms. Parasitology 131 (Suppl.), S19–S40.CrossRefGoogle ScholarPubMed
Saitou, N. and Nei, M. (1987). The neighbor-joining method: a new method for reconstructing phylogenetic trees. Molecular Biology and Evolution 4, 406–425.Google Scholar
Sattelle, D. B., Jones, A. K., Sattelle, B. M., Matsuda, K., Reenan, R. and Biggin, P. C. (2005). Edit, cut and paste in the nicotinic acetylcholine receptor gene family of Drosophila melanogaster. Bioessays 27, 366–376.CrossRefGoogle ScholarPubMed
Shimomura, M., Yokota, M., Matsuda, K., Sattelle, D. B. and Komai, K. (2004). Roles of loop C and the loop B-C interval of the nicotinic receptor alpha subunit in its selective interactions with imidacloprid in insects. Neuroscience Letters 363, 195–198.CrossRefGoogle Scholar
Sine, S. M. and Engel, A. G. (2006). Recent advances in Cys-loop receptor structure and function. Nature, London 440, 448–455.CrossRefGoogle ScholarPubMed
Swope, S. L., Moss, S. J., Raymond, L. A. and Huganir, R. L. (1999). Regulation of ligand-gated ion channels by protein phosphorylation. Advances in Second Messenger and Phosphoprotein Research 33, 49–78.CrossRefGoogle ScholarPubMed
Thompson, J. D., Gibson, T. J., Plewniak, F., Jeanmougin, F. and Higgins, D. G. (1997). The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Research 25, 4876–4882.CrossRefGoogle ScholarPubMed
Tomizawa, M., Millar, N. S. and Casida, J. E. (2005). Pharmacological profiles of recombinant and native insect nicotinic acetylcholine receptors. Insect Biochemistry and Molecular Biology 35, 1347–1355.CrossRefGoogle ScholarPubMed
Williams, B. M., Temburni, M. K., Bertrand, S., Bertrand, D. and Jacob, M. H. (1999). The long cytoplasmic loop of the alpha 3 subunit targets specific nAChR subtypes to synapses on neurons in vivo. Annals of the New York Academy of Sciences 868, 640–644.CrossRefGoogle Scholar