Insect nicotinic acetylcholine receptor gene families: From genetic model organism to vector, pest and beneficial species

MRC Functional Genetics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Le Gros Clark Building, South Parks Road, Oxford, OX1 3QX, UK.
Invertebrate Neuroscience (Impact Factor: 0.9). 04/2007; 7(1):67-73. DOI: 10.1007/s10158-006-0039-6
Source: PubMed

ABSTRACT Nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic transmission in the insect nervous system and are targets of a major group of insecticides, the neonicotinoids. Analyses of genome sequences have shown that nAChR gene families remain compact in diverse insect species, when compared to their mammalian counterparts. Thus, Drosophila melanogaster and Anopheles gambiae each possess 10 nAChR genes while Apis mellifera has 11. Although these are among the smallest nAChR gene families known, receptor diversity can be considerably increased by alternative splicing and mRNA A-to-I editing, thereby generating species-specific subunit isoforms. In addition, each insect possesses at least one highly divergent nAChR subunit. Species-specific subunit diversification may offer promising targets for future rational design of insecticides that act on particular pests while sparing beneficial insects. Electrophysiological studies on cultured Drosophila cholinergic neurons show partial agonist actions of the neonicotinoid imidacloprid and super-agonist actions of another neonicotinoid, clothianidin, on native nAChRs. Recombinant hybrid heteromeric nAChRs comprising Drosophila Dalpha2 and a vertebrate beta2 subunit have been instructive in mimicking such actions of imidacloprid and clothianidin. Unitary conductance measurements on native nAChRs indicate that more frequent openings of the largest conductance state may offer an explanation for the superagonist actions of clothianidin.

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    • "In our experiments, the nicotine-induced locomotor hyperactivity effect was blocked when mecamylamine, a non-selective nAChR antagonist [41], [42], was administered in addition to nicotine during the treatment and/or recording periods (Fig. 1B), demonstrating that nAChRs are necessary for cNILH. In Drosophila, the genes for ten nAChR subunits have been identified and are mainly expressed in the central nervous system (CNS) [43]. To determine which subunits mediate the chronic nicotine effects observed in our model system, we knocked-down the expression of eight of the nAChR subunits, one at a time, using an RNA-interfering (RNAi) approach [44] in the nervous system via a pan-neuronal GAL4, elav-GAL4. "
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    ABSTRACT: Long-term tobacco use causes nicotine dependence via the regulation of a wide range of genes and is accompanied by various health problems. Studies in mammalian systems have revealed some key factors involved in the effects of nicotine, including nicotinic acetylcholine receptors (nAChRs), dopamine and other neurotransmitters. Nevertheless, the signaling pathways that link nicotine-induced molecular and behavioral modifications remain elusive. Utilizing a chronic nicotine administration paradigm, we found that adult male fruit flies exhibited locomotor hyperactivity after three consecutive days of nicotine exposure, while nicotine-naive flies did not. Strikingly, this chronic nicotine-induced locomotor hyperactivity (cNILH) was abolished in Decapping Protein 2 or 1 (Dcp2 or Dcp1) -deficient flies, while only Dcp2-deficient flies exhibited higher basal levels of locomotor activity than controls. These results indicate that Dcp2 plays a critical role in the response to chronic nicotine exposure. Moreover, the messenger RNA (mRNA) level of Dcp2 in the fly head was suppressed by chronic nicotine treatment, and up-regulation of Dcp2 expression in the nervous system blocked cNILH. These results indicate that down-regulation of Dcp2 mediates chronic nicotine-exposure-induced locomotor hyperactivity in Drosophila. The decapping proteins play a major role in mRNA degradation; however, their function in the nervous system has rarely been investigated. Our findings reveal a significant role for the mRNA decapping pathway in developing locomotor hyperactivity in response to chronic nicotine exposure and identify Dcp2 as a potential candidate for future research on nicotine dependence.
    PLoS ONE 12/2012; 7(12):e52521. DOI:10.1371/journal.pone.0052521 · 3.23 Impact Factor
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    • "Nicotinic acetylcholine receptors (nAChRs) are excitatory neurotransmitter receptors that are found in both vertebrate and invertebrate species. In insects, nAChRs are expressed throughout the nervous system and are the site of action for economically important insecticides such as spinosyns and neonicotinoids [1,2]. Detailed information is available concerning the structure of nAChRs, as a consequence of studies conducted with receptors purified from the electric organ of the marine ray Torpedo[3] and from X-ray crystallographic studies conducted with nAChR fragments [4] and also with the closely related acetylcholine binding protein [5]. "
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    ABSTRACT: Nicotinic acetylcholine receptors (nAChRs) play an important role as excitatory neurotransmitters in vertebrate and invertebrate species. In insects, nAChRs are the site of action of commercially important insecticides and, as a consequence, there is considerable interest in examining their functional properties. However, problems have been encountered in the successful functional expression of insect nAChRs, although a number of strategies have been developed in an attempt to overcome such difficulties. Ten nAChR subunits have been identified in the model insect Drosophila melanogaster (Dα1-Dα7 and Dβ1-Dβ3) and a similar number have been identified in other insect species. The focus of the present study is the Dα5, Dα6 and Dα7 subunits, which are distinguished by their sequence similarity to one another and also by their close similarity to the vertebrate α7 nAChR subunit. A full-length cDNA clone encoding the Drosophila nAChR Dα5 subunit has been isolated and the properties of Dα5-, Dα6- and Dα7-containing nAChRs examined in a variety of cell expression systems. We have demonstrated the functional expression, as homomeric nAChRs, of the Dα5 and Dα7 subunits in Xenopus oocytes by their co-expression with the molecular chaperone RIC-3. Also, using a similar approach, we have demonstrated the functional expression of a heteromeric 'triplet' nAChR (Dα5 + Dα6 + Dα7) with substantially higher apparent affinity for acetylcholine than is seen with other subunit combinations. In addition, specific cell-surface binding of [125I]-α-bungarotoxin was detected in both Drosophila and mammalian cell lines when Dα5 was co-expressed with Dα6 and RIC-3. In contrast, co-expression of additional subunits (including Dα7) with Dα5 and Dα6 prevented specific binding of [125I]-α-bungarotoxin in cell lines, suggesting that co-assembly with other nAChR subunits can block maturation of correctly folded nAChRs in some cellular environments. Data are presented demonstrating the ability of the Drosophila Dα5 and Dα7 subunits to generate functional homomeric and also heteromeric nAChRs.
    BMC Neuroscience 06/2012; 13(1):73. DOI:10.1186/1471-2202-13-73 · 2.67 Impact Factor
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    • "A comparison of sequence identities between N. vitripennis, A. mellifera and D. melanogaster cys-loop LGIC subunits (Tables 1 and 2), as well as the use of a phylogenetic tree (Figure 3), indicates orthologous relationships between the wasp, honey bee and fruit fly subunits. To facilitate comparisons between the three species, Nasonia subunits were named after their Drosophila counterparts as previously done with Apis and Tribolium subunits (Jones and Sattelle, 2006, 2007). For example, the N. vitripennis orthologues of Drosophila, Da1, RDL and CG8916 were designated Nvita1, Nvit_RDL and Nvit_8916, respectively. "
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    ABSTRACT: Members of the cys-loop ligand-gated ion channel (cysLGIC) superfamily mediate chemical neurotransmission and are studied extensively as potential targets of drugs used to treat neurological disorders, such as Alzheimer's disease. Insect cys-loop LGICs also have central roles in the nervous system and are targets of highly successful insecticides. Here, we describe the cysLGIC superfamily of the parasitoid wasp, Nasonia vitripennis, which is emerging as a highly useful model organism and is deployed as a biological control of insect pests. The wasp superfamily consists of 26 genes, which is the largest insect cysLGIC superfamily characterized, whereas Drosophila melanogaster, Apis mellifera and Tribolium castaneum have 23, 21 and 24, respectively. As with Apis, Drosophila and Tribolium, Nasonia possesses ion channels predicted to be gated by acetylcholine, gamma-amino butyric acid, glutamate and histamine, as well as orthologues of the Drosophila pH-sensitive chloride channel (pHCl), CG8916 and CG12344. Similar to other insects, wasp cysLGIC diversity is broadened by alternative splicing and RNA A-to-I editing, which may also serve to generate species-specific receptor isoforms. These findings on N. vitripennis enhance our understanding of cysLGIC functional genomics and provide a useful basis for the study of their function in the wasp model, as well as for the development of improved insecticides that spare a major beneficial insect species.
    Heredity 03/2010; 104(3):247-59. DOI:10.1038/hdy.2009.97 · 3.81 Impact Factor
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