The nicotinic acetylcholine receptor gene family of the malaria mosquito, Anopheles gambiae

Jones, Andrew K.; Grauso, Marta; Sattelle, David B.

doi:10.1016/j.ygeno.2004.09.001

Cited by 113 publications

(143 citation statements)

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“…Insect genome projects have identified 10-12 nAChR subunits (Dupuis et a.l. 2012;Jones et al 2005;Jones et al 2006;Jones & Sattelle 2007;Millar 2003;Shao et al 2007;Tomizawa & Casida 2001). A search of the GenBank database (www.ncbi.…”

Section: Discussionmentioning

confidence: 99%

“…This may affect the receptor properties as phosphorylation of the TM3-TM4 intracellular loop regulates several aspects of receptor function, including desensitization and aggregation, and may affect the actions of ligands (Borges & Ferns 2001;Hopfield et al 1988;Jones & Sattelle 2010). Different forms generated by alternative splicing have also been observed in the α4 and α6 nAChR subunits (Gao et al 2007;Jones et al 2005;Jones et al 2006;Lansdell & Millar 2000a;Rinkevich & Scott 2009). Some subunits may produce not only isoforms but also truncated transcripts in several insects (Jones et al 2006;Saragoza et al 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Recent genome projects have revealed the total numbers of nAChR subunits in several insect species, including Drosophila melanogaster, Anopheles gambiae, Apis mellifera, Bombyx mori, and Tribolium castaneum (Dupuis et al 2012;Jones et al 2005;Jones et al 2006;Jones & Sattelle 2007Millar 2003;Shao et al 2007;Tomizawa & Casida 2001). Insect nAChRs exhibit unique characteristics, which are different from those of vertebrates.…”

Section: Introductionmentioning

confidence: 99%

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Five nicotinic acetylcholine receptor subunits from the Morotoge shrimp,Pandalopsis japonica: cloning, tissue distribution, and functional expression inXenopusoocytes

Kim

Yoon

Park

et al. 2015

Animal Cells and Systems

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The nicotinic acetylcholine receptor (nAChR) is a member of the ligand-gated ion channel (LGIC) family and is composed of five subunits arranged around a central pore. Expressed sequence tag screening and traditional cloning strategies revealed five full-length cDNAs encoding nAChR subunit homologs (Pajα3, Pajα10, Pajα11, Pajα12, and Pajβ1) in the Morotoge shrimp, Pandalopsis japonica. The nAChR subunits exhibited common structural characteristics, including a signal peptide sequence, a large N-terminal extracellular domain with conserved motifs for ligand binding (loops A-F), and a transmembrane (TM) domain with four hydrophobic TM motifs (TM1-TM4). Based on the conserved GEK motifs located just before TM2, all five nAChR subunits from P. japonica appear to be cation-selective ion channels. Among the five subunits, Pajα3 and Pajβ1 clustered together with insect core groups, whereas Pajα10, Pajα11, and Pajα12 were classified as a divergent group. Three distinct transcripts were identified in Pajα3, presumably due to alternative splicing between TM3 and TM4, which may be involved in channel formation with other subunits. All five nAChR subunits were expressed predominantly in neuronal tissues, including the brain, sinus gland/X-organ complex, thoracic ganglia, and abdominal ganglia, with no significant differences in subunit expression levels among the neuronal tissues. The five shrimp nAChR subunits could not be functionally expressed in Xenopus oocytes, but coexpression of Pajβ1 and rat α4 subunit (Rα4) formed functional channels responding to acetylcholine. Functional expression of vertebrate α subunit (Rα4) with invertebrate β1 subunit (Pajβ1) will expand our knowledge regarding the structural characteristics and molecular gating mechanism of invertebrate nAChRs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Five nicotinic acetylcholine receptor subunits from the Morotoge shrimp,Pandalopsis japonica: cloning, tissue distribution, and functional expression inXenopusoocytes

Kim

Yoon

Park

et al. 2015

Animal Cells and Systems

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“…In comparison to vertebrate nAChRs, insect gene families are relatively small with diversity created through alternative splicing (Jones et al, 2005;Lansdell and Millar, 2000). Insect nAChRs consist of of homopentameric α-subunits or heteropentameric α-and β-subunits that are highly conserved with greater than 60% identity between species and as high as 80% for the α1 subunit (Jones et al, 2007).…”

Section: κ-Hxtx-hv1c Prolongs Nachr Current Decaymentioning

confidence: 99%

Lethal effects of an insecticidal spider venom peptide involve positive allosteric modulation of insect nicotinic acetylcholine receptors

et al. 2017

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Please cite this article as: Windley, M.J., Vetter, I., Lewis, R.J., Nicholson, G.M., Lethal effects of an insecticidal spider venom peptide involve positive allosteric modulation of insect nicotinic acetylcholine receptors, Neuropharmacology (2017), doi: 10.1016/j.neuropharm.2017.04.008. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Highlights• The previously characterized BK Ca channel block is not responsible for the lethal excitatory toxicity of κ-HXTX-Hv1c • κ-HXTX-Hv1c is a positive allosteric modulator of the insect nicotinic acetylcholine receptor which acts by prolonging current decay and reversing receptor desensitization • The likely lethal target of κ-HXTX-Hv1c is the nicotinic acetylcholine receptor, acting by a mechanism similar to that of the insecticide spinosyn A. A B S T R A C Tκ-Hexatoxins (κ-HXTXs) are a family of excitotoxic insect-selective neurotoxins from Australian funnel-web spiders that are lethal to a wide range of insects, but display no toxicity towards vertebrates. The prototypic κ-HXTX-Hv1c selectively blocks native and expressed cockroach largeconductance calcium-activated potassium (BK Ca or K Ca 1.1) channels, but not their mammalian orthologs. Despite this potent and selective action on insect K Ca 1.1 channels, we found that the classical K Ca 1.1 blockers paxilline, charybdotoxin and iberiotoxin, which all block insect K Ca 1.1 channels, are not lethal in crickets. We therefore used whole-cell patch-clamp analysis of cockroach dorsal unpaired median (DUM) neurons to study the effects of κ-HXTX-Hv1c on sodium-activated (K Na ), delayed-rectifier (K DR ) and 'A-type' transient (K A ) K + channels. 1 µM κ-HXTX-Hv1c failed to significantly inhibit cockroach K Na and K DR channels, but did cause a 30 ± 7% saturating inhibition of K A channel currents, possibly via a Kv4 (Shal-like) action. However, this modest action at such a high concentration of κ-HXTX-Hv1c would indicate a different lethal target. Accordingly, we assessed the actions of κ-HXTX-Hv1c on neurotransmitter-gated ion channels in cockroach DUM neurons. We found that κ-HXTX-Hv1c failed to produce any major effects on GABA A or glutamate-Cl receptors but dramatically slowed nicotine-evoked ACh receptor (nAChR) current decay and reversed nAChR desensitization. These actions occurred without any alterations to nAChR current amplitude or the nicotine concentration-response curve, and are consistent with a positive allosteric modulation of nAChRs. κ-HXTX-Hv1c therefore represents the first venom peptide that selectively modulates insect nAChRs with a mode of action similar to the excitotoxic insecticide spino...

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“…Three of these four genes belong to nicotinic acetylcholine receptor gene families [19] which are the known targets of insecticides, neonicotinoids [20], as well as naturally derived spinisyns [21]. The presence of such high number of introns in these genes shows that they require more variability in their protein products and more number of introns make these genes more versatile in their expression by increasing the chances of alternative splicing and less 5′splice site biasness [22].…”

confidence: 99%

Fine-scale evolutionary genetic insights into Anopheles gambiae X-chromosome

Srivastava¹,

Dixit²,

Dash³

et al. 2009

JBiSE

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Understanding the genetic architecture of individual taxa of medical importance is the first step for designing disease preventive strategies. To understand the genetic details and evolutionary perspective of the model malaria vector, Anopheles gambiae and to use the information in other species of local importance, we scanned the published X-chromosome sequence for detail characterization and obtain evolutionary status of different genes. The telocentric X-chromosome contains 106 genes of known functions and 982 novel genes. Majorities of both the known and novel genes are with introns. The known genes are strictly biased towards less number of introns; about half of the total known genes have only one or two introns. The extreme sized (either long or short) genes were found to be most prevalent (58% short and 23% large). Statistically significant positive correlations between gene length and intron length as well as with intron number and intron length were obtained signifying the role of introns in contributing to the overall size of the known genes of X-chromosome in An. gambiae. We compared each individual gene of An. gambiae with 33 other taxa having whole genome sequence information. In general, the mosquito Aedes aegypti was found to be genetically closest and the yeast Saccharomyces cerevisiae as most distant taxa to An. gambiae. Further, only about a quarter of the known genes of X-chromosome were unique to An. gambiae and majorities have orthologs in different taxa. A phylogenetic tree was constructed based on a single gene found to be highly orthologous across all the 34 taxa. Evolutionary relationships among 13 different taxa were inferred which corroborate the previous and present findings on genetic relationships across various taxa.

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The nicotinic acetylcholine receptor gene family of the malaria mosquito, Anopheles gambiae

Cited by 113 publications

References 51 publications

Five nicotinic acetylcholine receptor subunits from the Morotoge shrimp,Pandalopsis japonica: cloning, tissue distribution, and functional expression inXenopusoocytes

Five nicotinic acetylcholine receptor subunits from the Morotoge shrimp,Pandalopsis japonica: cloning, tissue distribution, and functional expression inXenopusoocytes

Lethal effects of an insecticidal spider venom peptide involve positive allosteric modulation of insect nicotinic acetylcholine receptors

Fine-scale evolutionary genetic insights into Anopheles gambiae X-chromosome

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