Nicotinic Acetylcholine Receptors in the NematodeCaenorhabditis elegans

Ballivet, Marc; Alliod, Christine; Bertrand, Sonia; Bertrand, Daniel

doi:10.1006/jmbi.1996.0248

Cited by 105 publications

(125 citation statements)

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“…For example, the hitherto elusive steroid site on the GABA receptor was identified in a comprehensive comparison between Drosophila melanogaster GABA-gated chloride channels and human GABA A type receptors [16]. We have previously shown that the anthelmintic compound, IVM, enhanced ACh-induced 7 amplitude responses, confirming the earlier finding of Bertrand and colleagues [17], while slightly attenuating responses of ACR-16 [18] , a Caenorhabditis elegans α7 homologue [19,20]. ACR-16 and 7 nAChR subunits share considerable amino acid sequence identity of 47% but show important differences in residues considered important in allosteric drug actions (Fig.…”

Section: Page 4 Of 26supporting

confidence: 76%

Comparative pharmacology and computational modelling yield insights into allosteric modulation of human α7 nicotinic acetylcholine receptors

Sattelle

Akamatsu²,

Matsuda³

et al. 2009

Biochemical Pharmacology

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HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. 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.

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Section: Page 4 Of 26supporting

confidence: 76%

Comparative pharmacology and computational modelling yield insights into allosteric modulation of human α7 nicotinic acetylcholine receptors

Sattelle

Akamatsu²,

Matsuda³

et al. 2009

Biochemical Pharmacology

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“…Injection of ACR-16 cDNA alone was reported to produce functional AChRs in Xenopus oocytes, yet yielding only small currents (usually Ͻ200 nA at Ϫ100 mV) (10,18). Because ric-3 was demonstrated to be essential in vivo for N-AChR expression (13), we coinjected acr-16 and ric-3 cRNAs.…”

Section: Resultsmentioning

confidence: 99%

“…3B). This inhibition likely resulted from openchannel block by the positively charged levamisole molecule (10,25,26). To test this hypothesis, we performed voltage ramps and demonstrated that 500 M levamisole produced a slight voltagedependent block of L-AChR responses (Fig.…”

Section: L-achrs Are Permeable To Calcium and Do Not Show Macroscopicmentioning

confidence: 99%

“…This receptor contains the subunit ACR-16, which is closely related to the vertebrate ␣7 gene. ACR-16 forms functional homomeric AChRs when expressed in Xenopus oocytes (10). L-AChRs and N-AChRs are partially redundant because disruption of either receptor causes no or weak locomotory defects, whereas disruption of both receptors causes almost complete paralysis of the animal (11,12).…”

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confidence: 99%

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Eight genes are required for functional reconstitution of the Caenorhabditis elegans levamisole-sensitive acetylcholine receptor

Boulin

Gielen

Richmond

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

177

311

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Levamisole-sensitive acetylcholine receptors (L-AChRs) are ligandgated ion channels that mediate excitatory neurotransmission at the neuromuscular junctions of nematodes. They constitute a major drug target for anthelminthic treatments because they can be activated by nematode-specific cholinergic agonists such as levamisole. Genetic screens conducted in Caenorhabditis elegans for resistance to levamisole toxicity identified genes that are indispensable for the biosynthesis of L-AChRs. These include 5 genes encoding distinct AChR subunits and 3 genes coding for ancillary proteins involved in assembly and trafficking of the receptors. Despite extensive analysis of L-AChRs in vivo, pharmacological and biophysical characterization of these receptors has been greatly hampered by the absence of a heterologous expression system. Using Xenopus laevis oocytes, we were able to reconstitute functional L-AChRs by coexpressing the 5 distinct receptor subunits and the 3 ancillary proteins. Strikingly, this system recapitulates the genetic requirements for receptor expression in vivo because omission of any of these 8 genes dramatically impairs L-AChR expression. We demonstrate that 3 ␣-and 2 non-␣-subunits assemble into the same receptor. Pharmacological analysis reveals that the prototypical cholinergic agonist nicotine is unable to activate L-AChRs but rather acts as a potent allosteric inhibitor. These results emphasize the role of ancillary proteins for efficient expression of recombinant neurotransmitter receptors and open the way for in vitro screening of novel anthelminthic agents.anthelminthic drug ͉ recombinant receptor expression

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“…In addition, Xenopus oocytes have been used successfully to examine nAChR subunits cloned from several invertebrate species, including the aphid Myzus persicae [89], the brown planthopper Nilaparvata lugens [90], the fruit fly Drosophila melanogaster [69,91], the locust Schistocerca gregaria [92] and the nematode Caenorhabditis elegans [93,94]. Frustratingly, the heterologous expression of invertebrate nAChRs has proved to be extremely difficult [59,95] and, in several instances, this has often been achieved only by co-expression with vertebrate nAChR subunits [65,91,96,97].…”

Section: Expression Of Recombinant Nachrs In Xenopus Oocytesmentioning

confidence: 99%

A review of experimental techniques used for the heterologous expression of nicotinic acetylcholine receptors

Millar

2009

Biochemical Pharmacology

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Nicotinic acetylcholine receptors (nAChRs) are members of the Cys-loop family of neurotransmitter-gated ion channels, a family that also includes receptors for γ-aminobutyric acid, glycine and 5-hydroxytryptamine. In humans, nAChRs have been implicated in several neurological and psychiatric disorders and are major targets for pharmaceutical drug discovery. In addition, nAChRs are important targets for neuroactive pesticides in insects and in other invertebrates. Historically, nAChRs have been one of the most intensively studied families of neurotransmitter receptors. They were the first neurotransmitter receptors to be biochemically purified and the first to be characterized by molecular cloning and heterologous expression. Although much has been learnt from studies of native nAChRs, the expression of recombinant nAChRs has provided dramatic advances in the characterization of these important receptors. This review will provide a brief history of the characterization of nAChRs by heterologous expression. It will focus, in particular, upon studies of recombinant nAChRs, work that has been conducted by many hundreds of scientists during a period of almost 30 years since the molecular cloning of nAChR subunits in the early 1980's.

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Nicotinic Acetylcholine Receptors in the NematodeCaenorhabditis elegans

Cited by 105 publications

References 0 publications

Comparative pharmacology and computational modelling yield insights into allosteric modulation of human α7 nicotinic acetylcholine receptors

Comparative pharmacology and computational modelling yield insights into allosteric modulation of human α7 nicotinic acetylcholine receptors

Eight genes are required for functional reconstitution of the Caenorhabditis elegans levamisole-sensitive acetylcholine receptor

A review of experimental techniques used for the heterologous expression of nicotinic acetylcholine receptors

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