| pubmed-article:19020092 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19020092 | lifeskim:mentions | umls-concept:C0017337 | lld:lifeskim |
| pubmed-article:19020092 | lifeskim:mentions | umls-concept:C0034792 | lld:lifeskim |
| pubmed-article:19020092 | lifeskim:mentions | umls-concept:C0205245 | lld:lifeskim |
| pubmed-article:19020092 | lifeskim:mentions | umls-concept:C0162610 | lld:lifeskim |
| pubmed-article:19020092 | lifeskim:mentions | umls-concept:C1546857 | lld:lifeskim |
| pubmed-article:19020092 | lifeskim:mentions | umls-concept:C1556066 | lld:lifeskim |
| pubmed-article:19020092 | lifeskim:mentions | umls-concept:C1619636 | lld:lifeskim |
| pubmed-article:19020092 | lifeskim:mentions | umls-concept:C1514873 | lld:lifeskim |
| pubmed-article:19020092 | pubmed:issue | 47 | lld:pubmed |
| pubmed-article:19020092 | pubmed:dateCreated | 2008-11-26 | lld:pubmed |
| pubmed-article:19020092 | pubmed:abstractText | Levamisole-sensitive acetylcholine receptors (L-AChRs) are ligand-gated 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 alpha- and 2 non-alpha-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. | lld:pubmed |
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| pubmed-article:19020092 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19020092 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19020092 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:19020092 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19020092 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:19020092 | pubmed:issn | 1091-6490 | lld:pubmed |
| pubmed-article:19020092 | pubmed:author | pubmed-author:WilliamsDanie... | lld:pubmed |
| pubmed-article:19020092 | pubmed:author | pubmed-author:PaolettiPierr... | lld:pubmed |
| pubmed-article:19020092 | pubmed:author | pubmed-author:RichmondJanet... | lld:pubmed |
| pubmed-article:19020092 | pubmed:author | pubmed-author:BoulinThomasT | lld:pubmed |
| pubmed-article:19020092 | pubmed:author | pubmed-author:BessereauJean... | lld:pubmed |
| pubmed-article:19020092 | pubmed:author | pubmed-author:GielenMarcM | lld:pubmed |
| pubmed-article:19020092 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19020092 | pubmed:day | 25 | lld:pubmed |
| pubmed-article:19020092 | pubmed:volume | 105 | lld:pubmed |
| pubmed-article:19020092 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19020092 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19020092 | pubmed:pagination | 18590-5 | lld:pubmed |
| pubmed-article:19020092 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
| pubmed-article:19020092 | pubmed:meshHeading | pubmed-meshheading:19020092... | lld:pubmed |
| pubmed-article:19020092 | pubmed:meshHeading | pubmed-meshheading:19020092... | lld:pubmed |
| pubmed-article:19020092 | pubmed:meshHeading | pubmed-meshheading:19020092... | lld:pubmed |
| pubmed-article:19020092 | pubmed:meshHeading | pubmed-meshheading:19020092... | lld:pubmed |
| pubmed-article:19020092 | pubmed:meshHeading | pubmed-meshheading:19020092... | lld:pubmed |
| pubmed-article:19020092 | pubmed:meshHeading | pubmed-meshheading:19020092... | lld:pubmed |
| pubmed-article:19020092 | pubmed:year | 2008 | lld:pubmed |
| pubmed-article:19020092 | pubmed:articleTitle | Eight genes are required for functional reconstitution of the Caenorhabditis elegans levamisole-sensitive acetylcholine receptor. | lld:pubmed |
| pubmed-article:19020092 | pubmed:affiliation | Ecole Normale Supérieure, Biology Department, 75005 Paris, France. | lld:pubmed |
| pubmed-article:19020092 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:19020092 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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