Functional Characterization of a Novel Class of Morantel-Sensitive Acetylcholine Receptors in Nematodes
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{"title"=>"Functional Characterization of a Novel Class of Morantel-Sensitive Acetylcholine Receptors in Nematodes", "type"=>"journal", "authors"=>[{"first_name"=>"Elise", "last_name"=>"Courtot", "scopus_author_id"=>"56031744900"}, {"first_name"=>"Claude L.", "last_name"=>"Charvet", "scopus_author_id"=>"9242379300"}, {"first_name"=>"Robin N.", "last_name"=>"Beech", "scopus_author_id"=>"7006817292"}, {"first_name"=>"Abdallah", "last_name"=>"Harmache", "scopus_author_id"=>"6508115822"}, {"first_name"=>"Adrian J.", "last_name"=>"Wolstenholme", "scopus_author_id"=>"7003753272"}, {"first_name"=>"Lindy", "last_name"=>"Holden-Dye", "scopus_author_id"=>"7003815028"}, {"first_name"=>"Vincent", "last_name"=>"O’Connor", "scopus_author_id"=>"57039211600"}, {"first_name"=>"Nicolas", "last_name"=>"Peineau", "scopus_author_id"=>"6603031314"}, {"first_name"=>"Debra J.", "last_name"=>"Woods", "scopus_author_id"=>"16744513300"}, {"first_name"=>"Cedric", "last_name"=>"Neveu", "scopus_author_id"=>"7003309499"}], "year"=>2015, "source"=>"PLoS Pathogens", "identifiers"=>{"issn"=>"15537374", "scopus"=>"2-s2.0-84953278168", "sgr"=>"84953278168", "pui"=>"607577444", "pmid"=>"26625142", "doi"=>"10.1371/journal.ppat.1005267"}, "id"=>"30acd698-e3b9-3743-93cf-0137954e3302", "abstract"=>"Acetylcholine receptors are pentameric ligand-gated channels involved in excitatory neuro-transmission in both vertebrates and invertebrates. In nematodes, they represent major targets for cholinergic agonist or antagonist anthelmintic drugs. Despite the large diversity of acetylcholine-receptor subunit genes present in nematodes, only a few receptor subtypes have been characterized so far. Interestingly, parasitic nematodes affecting human or animal health possess two closely related members of this gene family, acr-26 and acr-27 that are essentially absent in free-living or plant parasitic species. Using the pathogenic parasitic nematode of ruminants, Haemonchus contortus, as a model, we found that Hco-ACR-26 and Hco-ACR-27 are co-expressed in body muscle cells. We demonstrated that co-expression of Hco-ACR-26 and Hco-ACR-27 in Xenopus laevis oocytes led to the functional expression of an acetylcholine-receptor highly sensitive to the anthelmintics morantel and pyrantel. Importantly we also reported that ACR-26 and ACR-27, from the distantly related parasitic nematode of horses, Parascaris equorum, also formed a functional acetylcholine-receptor highly sensitive to these two drugs. In Caenorhabditis elegans, a free-living model nematode, we demonstrated that heterologous expression of the H. contortus and P. equorum receptors drastically increased its sensitivity to morantel and pyrantel, mirroring the pharmacological properties observed in Xenopus oocytes. Our results are the first to describe significant molecular determinants of a novel class of nematode body wall muscle AChR.", "link"=>"http://www.mendeley.com/research/functional-characterization-novel-class-morantelsensitive-acetylcholine-receptors-nematodes-2", "reader_count"=>8, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>3, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>3, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Medicine and Dentistry"=>1, "Agricultural and Biological Sciences"=>4, "Neuroscience"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Unspecified"=>{"Unspecified"=>2}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2595400"], "description"=>"<p>Tree was built upon an alignment of AChR subunit sequences excluding the predicted signal peptide and the highly variable region between TM3 and TM4. Potential homologs of ACR-26 identified in the molluscs, <i>Aplysia californica</i>, <i>Crassostrea gigas</i>, <i>Lottia gigantean</i>, the annelid <i>Capitella telata</i> and the arthropods <i>Ixodes scapularis</i> and <i>Daphnia pulex</i> were also included in the analysis. The tree was rooted with DEG-3 group subunit sequences. Branch lengths are proportional to the number of substitutions per amino acid. Scale bar represents the number of substitution per site. Red dots at the nodes indicate bootstrap values >70%. Accession numbers for sequences used in the phylogenetic analysis are provided in Materials and Methods section. <i>C</i>. <i>elegans</i> AChR subunit groups were named as proposed by Mongan <i>et al</i>. [<a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005267#ppat.1005267.ref035\" target=\"_blank\">35</a>]. The three letter prefixes in AChR subunit gene names, <i>Cel</i>, <i>Tci</i>, <i>Hco</i>, <i>Aca</i>, <i>Tca</i>, <i>Peq</i>, <i>Ovo</i>, <i>Dim</i>, <i>Llo</i>, <i>Bma</i>, <i>Sra and Ptr</i> refer to <i>Caenorhabditis elegans</i>, <i>Teladorsagia circumcincta</i>, <i>Haemonchus contortus</i>, <i>Ancylostoma caninum</i>, <i>Toxocara canis</i>, <i>Parascaris equorum</i>, <i>Onchocerca volvulus</i>, <i>Dirofilaria immitis</i>, <i>Loa loa</i>, <i>Brugia malayi</i>, <i>Strongyloides ratti</i> and <i>Parastrogyloides trichosuri</i> respectively. Parasitic nematode species belonging to Clade III, VI and V are highlighted in red, green and blue respectively.</p>", "links"=>[], "tags"=>["equorum receptors", "nematode body wall muscle AChR", "Caenorhabditis elegans", "Nematodes Acetylcholine receptors", "Xenopus laevis oocytes", "cholinergic agonist", "novel class", "acr", "heterologous expression", "gene family", "receptor subtypes", "anthelmintics morantel", "animal health", "antagonist anthelmintic drugs", "Xenopus oocytes", "body muscle cells", "Haemonchus contortus", "Functional Characterization", "Parascaris equorum"], "article_id"=>1614988, "categories"=>["Biological Sciences"], "users"=>["Elise Courtot", "Claude L. Charvet", "Robin N. Beech", "Abdallah Harmache", "Adrian J. Wolstenholme", "Lindy Holden-Dye", "Vincent O’Connor", "Nicolas Peineau", "Debra J. Woods", "Cedric Neveu"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005267.g001", "stats"=>{"downloads"=>5, "page_views"=>39, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Maximum_likelihood_tree_showing_relationships_of_ACR_26_and_ACR_27_acetylcholine_receptor_AChR_subunits_from_parasitic_nematodes_with_C_elegans_AChR_subunits_/1614988", "title"=>"Maximum likelihood tree showing relationships of ACR-26 and ACR-27 acetylcholine receptor (AChR) subunits from parasitic nematodes with <i>C</i>. <i>elegans</i> AChR subunits.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-01 02:49:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/2595403"], "description"=>"<p><i>acr-26</i> and <i>acr-27</i> deduced amino-acid sequences from <i>Haemonchus contortus</i> and <i>Parascaris equorum</i> were aligned using the MUSCLE algorithm [<a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1005267#ppat.1005267.ref036\" target=\"_blank\">36</a>] and further processed using GeneDoc. Predicted signal peptide sequences are shaded in grey. Amino acids conserved between ACR-26 and ACR-27 sequences are highlighted in red. Amino acids specifically shared by ACR-26 homologs are highlighted in dark blue. Amino acids specifically shared by ACR-27 homologs are highlighted in light blue. The cys-loop, the four transmembrane regions (TM1–TM4) and the primary agonist binding (YxCC) which is present in ACR-26 homologs but absent in ACR-27 homologs are noted above the sequences. Hco (<i>Haemonchus contortus</i>), Peq (<i>Parascaris equorum</i>).</p>", "links"=>[], "tags"=>["equorum receptors", "nematode body wall muscle AChR", "Caenorhabditis elegans", "Nematodes Acetylcholine receptors", "Xenopus laevis oocytes", "cholinergic agonist", "novel class", "acr", "heterologous expression", "gene family", "receptor subtypes", "anthelmintics morantel", "animal health", "antagonist anthelmintic drugs", "Xenopus oocytes", "body muscle cells", "Haemonchus contortus", "Functional Characterization", "Parascaris equorum"], "article_id"=>1614991, "categories"=>["Biological Sciences"], "users"=>["Elise Courtot", "Claude L. Charvet", "Robin N. Beech", "Abdallah Harmache", "Adrian J. Wolstenholme", "Lindy Holden-Dye", "Vincent O’Connor", "Nicolas Peineau", "Debra J. Woods", "Cedric Neveu"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005267.g002", "stats"=>{"downloads"=>0, "page_views"=>40, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Amino_acid_alignments_of_ACR_26_and_ACR_27_AChR_subunit_sequences_from_Haemonchus_contortus_and_Parascaris_equorum_/1614991", "title"=>"Amino-acid alignments of ACR-26 and ACR-27 AChR subunit sequences from <i>Haemonchus contortus</i> and <i>Parascaris equorum</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-01 02:49:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/2595404"], "description"=>"<p><b>(A)</b> Transcription of <i>Hco-acr-26</i> and <i>Hco-acr-27</i> throughout the <i>H</i>. <i>contortus</i> lifecycle as revealed by RT-PCR experiments. ω: embryonated egg; L2: second stage larvae; L3: ensheated third stage larvae; XL3: <i>in vitro</i> exsheated third stage larvae, L4: fourth stage larvae; m: adult males; f: adult females. Integrity of cDNA preparations was verified by PCR using primers designed to amplify a 380 bp fragment of the <i>H</i>. <i>contortus</i> gapdh cDNA. <b>(B)</b> Relative mRNA expression levels of <i>Hco-acr-26</i> and <i>Hco-acr-27</i> in <i>H</i>. <i>contortus</i> L3 and adult males. Real-time RT-PCR experiments were performed in triplicate for third stage larvae (L3) and adult males corresponding to free-living and parasitic stage respectively. Each set of experiments was repeated twice using two independent cDNAs templates. The mRNA expression level for <i>Hco-acr-26</i> was normalized to 1. The mRNA fold changes were calculated using three distinct reference genes encoding for gapdh, actin and β-tubulin. The data are presented as fold changes in mean ± SEM of mRNA expression. No difference was observed between relative mRNA expression of <i>Hco-acr-26</i> and <i>Hco-acr-27</i> in L3 and adult males (paired Student’s t-test).</p>", "links"=>[], "tags"=>["equorum receptors", "nematode body wall muscle AChR", "Caenorhabditis elegans", "Nematodes Acetylcholine receptors", "Xenopus laevis oocytes", "cholinergic agonist", "novel class", "acr", "heterologous expression", "gene family", "receptor subtypes", "anthelmintics morantel", "animal health", "antagonist anthelmintic drugs", "Xenopus oocytes", "body muscle cells", "Haemonchus contortus", "Functional Characterization", "Parascaris equorum"], "article_id"=>1614992, "categories"=>["Biological Sciences"], "users"=>["Elise Courtot", "Claude L. Charvet", "Robin N. Beech", "Abdallah Harmache", "Adrian J. Wolstenholme", "Lindy Holden-Dye", "Vincent O’Connor", "Nicolas Peineau", "Debra J. Woods", "Cedric Neveu"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005267.g003", "stats"=>{"downloads"=>2, "page_views"=>47, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_monitoring_of_Hco_acr_26_and_Hco_acr_27_in_Haemonchus_contortus_/1614992", "title"=>"Expression monitoring of <i>Hco-acr-26</i> and <i>Hco-acr-27</i> in <i>Haemonchus contortus</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-01 02:49:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/2595405"], "description"=>"<p>XL3 larvae of <i>H</i>. <i>contortus</i> were fixed and hybridized with digoxygenin labeled antisense cDNA probes to monitor the localization of <i>Hco-acr-26</i><b>(panel A)</b> and <i>Hco-acr-27</i> mRNAs <b>(panel B)</b> within the worm. Sense probes were used as negative control. cDNA/mRNA hybridomes were detected using primary anti-digoxygenin antibodies in combination with secondary Alexa 594-labeled antibodies (red). Body wall muscular cells were stained using primary antibodies raised against the myosin protein and further revealed with secondary Alexa 488-labeled antibodies (green). The scale bars correspond to 20 μm.</p>", "links"=>[], "tags"=>["equorum receptors", "nematode body wall muscle AChR", "Caenorhabditis elegans", "Nematodes Acetylcholine receptors", "Xenopus laevis oocytes", "cholinergic agonist", "novel class", "acr", "heterologous expression", "gene family", "receptor subtypes", "anthelmintics morantel", "animal health", "antagonist anthelmintic drugs", "Xenopus oocytes", "body muscle cells", "Haemonchus contortus", "Functional Characterization", "Parascaris equorum"], "article_id"=>1614993, "categories"=>["Biological Sciences"], "users"=>["Elise Courtot", "Claude L. Charvet", "Robin N. Beech", "Abdallah Harmache", "Adrian J. Wolstenholme", "Lindy Holden-Dye", "Vincent O’Connor", "Nicolas Peineau", "Debra J. Woods", "Cedric Neveu"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005267.g004", "stats"=>{"downloads"=>2, "page_views"=>33, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_In_situ_hybridizations_of_Hco_acr_26_and_Hco_acr_27_mRNAs_in_H_contortus_/1614993", "title"=>"<i>In-situ</i> hybridizations of <i>Hco-acr-26</i> and <i>Hco-acr-27</i> mRNAs in <i>H</i>. <i>contortus</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-01 02:49:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/2595406"], "description"=>"<p><i>H</i>. <i>contortus</i> L2 larval stage and adult males were fixed and incubated with affinity-purified antibodies raised against Hco-ACR-26 and Hco-ACR-27 subunits. Alexa 594- and Alexa 488- labeled secondary antibodies were used to determine the localization of Hco-ACR-26 (red) and Hco-ACR-27 (green) respectively. <b>(A and B)</b> Transmitted light and corresponding fluorescent apotome imaging performed on <i>H</i>. <i>contortus</i> L2 stage. Nematode’s nuclei were stained in blue using DAPI. <b>Panel A</b> shows a staining for Hco-ACR-26 and Hco-ACR-27 in striated cells of the nematode. <b>Panel B</b> shows that in a deeper focal section, Hco-ACR-26 and Hco-ACR-27 were also found to be expressed in another tissue potentially corresponding to the nerve ring (white arrows). <b>(C, D and E)</b> Confocal microscopy performed on L2 stage <b>(C and E)</b> and cross section of adult males <b>(D)</b>. Body wall muscle cells were stained using primary antibodies raised against the myosin protein and further revealed with secondary Alexa 350-labeled antibodies (blue). <b>(E)</b> Negative control performed with anti-Hco-ACR-26 and anti-Hco-ACR-27 pre-adsorbed with their respective peptide antigen. For A, B, C and E anterior region is to the right. The scale bars correspond to 20 μm.</p>", "links"=>[], "tags"=>["equorum receptors", "nematode body wall muscle AChR", "Caenorhabditis elegans", "Nematodes Acetylcholine receptors", "Xenopus laevis oocytes", "cholinergic agonist", "novel class", "acr", "heterologous expression", "gene family", "receptor subtypes", "anthelmintics morantel", "animal health", "antagonist anthelmintic drugs", "Xenopus oocytes", "body muscle cells", "Haemonchus contortus", "Functional Characterization", "Parascaris equorum"], "article_id"=>1614994, "categories"=>["Biological Sciences"], "users"=>["Elise Courtot", "Claude L. Charvet", "Robin N. Beech", "Abdallah Harmache", "Adrian J. Wolstenholme", "Lindy Holden-Dye", "Vincent O’Connor", "Nicolas Peineau", "Debra J. Woods", "Cedric Neveu"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005267.g005", "stats"=>{"downloads"=>1, "page_views"=>57, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunolocalization_of_Hco_ACR_26_and_Hco_ACR_27_in_H_contortus_/1614994", "title"=>"Immunolocalization of Hco-ACR-26 and Hco-ACR-27 in <i>H</i>. <i>contortus</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-01 02:49:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/2595407"], "description"=>"<p>For both parasitic nematode species, the robust expression of functional AChRs required the co-injection of cRNAs corresponding to ACR-26 and ACR-27 AChR subunits in combination with the three ancillary factors RIC-3.1; UNC-50 and UNC-74. Currents were measured at the plateau. <b>(A)</b> Average plateau values for co-injection of all cRNAs were 161.4±18.67 nA (n = 41) for <i>H</i>. <i>contortus</i> receptor. <b>(B)</b> Average plateau values for co-injection of all cRNAs were 246.8±33.39 nA (n = 37) for <i>P</i>. <i>equorum</i> receptor. Results are shown in mean ± SEM.</p>", "links"=>[], "tags"=>["equorum receptors", "nematode body wall muscle AChR", "Caenorhabditis elegans", "Nematodes Acetylcholine receptors", "Xenopus laevis oocytes", "cholinergic agonist", "novel class", "acr", "heterologous expression", "gene family", "receptor subtypes", "anthelmintics morantel", "animal health", "antagonist anthelmintic drugs", "Xenopus oocytes", "body muscle cells", "Haemonchus contortus", "Functional Characterization", "Parascaris equorum"], "article_id"=>1614995, "categories"=>["Biological Sciences"], "users"=>["Elise Courtot", "Claude L. Charvet", "Robin N. Beech", "Abdallah Harmache", "Adrian J. Wolstenholme", "Lindy Holden-Dye", "Vincent O’Connor", "Nicolas Peineau", "Debra J. Woods", "Cedric Neveu"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005267.g006", "stats"=>{"downloads"=>0, "page_views"=>28, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Identification_of_the_minimal_subunit_combination_and_ancillary_proteins_required_for_the_functional_expression_in_Xenopus_oocyte_of_AChR_containing_ACR_26_and_ACR_27_from_H_contortus_and_P_equorum_/1614995", "title"=>"Identification of the minimal subunit combination and ancillary proteins required for the functional expression in <i>Xenopus</i> oocyte of AChR containing ACR-26 and ACR-27 from <i>H</i>. <i>contortus</i> and <i>P</i>. <i>equorum</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-01 02:49:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/2595408"], "description"=>"<p>(A and B) Representative recording traces from a single oocyte expressing Hco-26/27 (A) or Peq-26/27 (B) challenged with 100 μM ACh and 100 μM of different anthelmintic compounds (morantel (Mor), pyrantel (Pyr), oxantel (Oxa), levamisole (Lev), bephenium (Beph) and nicotine (Nic)). The bars indicate the time period of the agonist application. (C and D) Scatter plot (mean ± SEM) of normalized currents elicited by 100 μM of anthelmintic compounds on Hco-26/27 (C) or Peq-26/27 (D). Currents have been normalized to and compared with 100 μM ACh currents. Paired Student’s t-test, ***p<0.001. (E) Dose-response relationships of Hco-26/27 for the agonists ACh (black circle, n = 6), Mor (red squares, n = 8) and Pyr (blue triangles, n = 6). Responses are all normalized to the response to 1 mM acetylcholine. EC<sub>50</sub> are 80.1±1.1 μM, 29.0±1.3 μM and 6.8±1.3 μM for ACh, Mor and Pyr respectively. (F) Dose-response relationships of Peq-26/27 for the agonists ACh (black circle, n = 7), Mor (red squares, n = 9), Pyr (blue triangles, n = 10) and Lev (green lozenges, n = 6). Responses are all normalized to the response to 1 mM acetylcholine. EC<sub>50</sub> are 34.9±1.1 μM; 0.32±0.26 μM; 0.98±0.26 μM and 16.7±1.3 μM for ACh, Mor, Pyr and Lev respectively.</p>", "links"=>[], "tags"=>["equorum receptors", "nematode body wall muscle AChR", "Caenorhabditis elegans", "Nematodes Acetylcholine receptors", "Xenopus laevis oocytes", "cholinergic agonist", "novel class", "acr", "heterologous expression", "gene family", "receptor subtypes", "anthelmintics morantel", "animal health", "antagonist anthelmintic drugs", "Xenopus oocytes", "body muscle cells", "Haemonchus contortus", "Functional Characterization", "Parascaris equorum"], "article_id"=>1614996, "categories"=>["Biological Sciences"], "users"=>["Elise Courtot", "Claude L. Charvet", "Robin N. Beech", "Abdallah Harmache", "Adrian J. Wolstenholme", "Lindy Holden-Dye", "Vincent O’Connor", "Nicolas Peineau", "Debra J. Woods", "Cedric Neveu"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005267.g007", "stats"=>{"downloads"=>1, "page_views"=>60, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pharmacological_profiles_of_Hco_26_27_and_Peq_26_27_/1614996", "title"=>"Pharmacological profiles of Hco-26/27 and Peq-26/27.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-01 02:49:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/2595409"], "description"=>"<p>Thrashing assays were performed during 30 minutes with t0 corresponding to basal movements. For each <i>C</i>. <i>elegans</i> expressing parasitic nematode ACR-26 or ACR-27 alone or in combination, two independent lines were used with >12 worms per lines. Thrashing assays performed with 40 μM morantel on N2 (WT) and transformed worms expressing ACR-26 and ACR-27 subunits (alone or in combination) from <i>H</i>. <i>contortus</i> (A) or <i>P</i>. <i>equorum</i> (B). All results are expressed as mean ± SEM. Using <i>C</i>. <i>elegans</i> N2 as reference, statistical analysis was performed using the One-Way ANOVA with Tukey’s Multiple Comparison Test with ***p<0.001, NS, not significant.</p>", "links"=>[], "tags"=>["equorum receptors", "nematode body wall muscle AChR", "Caenorhabditis elegans", "Nematodes Acetylcholine receptors", "Xenopus laevis oocytes", "cholinergic agonist", "novel class", "acr", "heterologous expression", "gene family", "receptor subtypes", "anthelmintics morantel", "animal health", "antagonist anthelmintic drugs", "Xenopus oocytes", "body muscle cells", "Haemonchus contortus", "Functional Characterization", "Parascaris equorum"], "article_id"=>1614997, "categories"=>["Biological Sciences"], "users"=>["Elise Courtot", "Claude L. Charvet", "Robin N. Beech", "Abdallah Harmache", "Adrian J. Wolstenholme", "Lindy Holden-Dye", "Vincent O’Connor", "Nicolas Peineau", "Debra J. Woods", "Cedric Neveu"], "doi"=>"https://dx.doi.org/10.1371/journal.ppat.1005267.g008", "stats"=>{"downloads"=>1, "page_views"=>42, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Co_expression_of_ACR_26_and_ACR_27_in_C_elegans_increases_its_morantel_sensitivity_/1614997", "title"=>"Co-expression of ACR-26 and ACR-27 in <i>C</i>. <i>elegans</i> increases its morantel sensitivity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-12-01 02:49:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/2595417", "https://ndownloader.figshare.com/files/2595418", "https://ndownloader.figshare.com/files/2595419", "https://ndownloader.figshare.com/files/2595420", "https://ndownloader.figshare.com/files/2595421", "https://ndownloader.figshare.com/files/2595422", "https://ndownloader.figshare.com/files/2595423", "https://ndownloader.figshare.com/files/2595424"], "description"=>"<div><p>Acetylcholine receptors are pentameric ligand–gated channels involved in excitatory neuro-transmission in both vertebrates and invertebrates. In nematodes, they represent major targets for cholinergic agonist or antagonist anthelmintic drugs. Despite the large diversity of acetylcholine-receptor subunit genes present in nematodes, only a few receptor subtypes have been characterized so far. Interestingly, parasitic nematodes affecting human or animal health possess two closely related members of this gene family, <i>acr-26</i> and <i>acr-27</i> that are essentially absent in free-living or plant parasitic species. Using the pathogenic parasitic nematode of ruminants, <i>Haemonchus contortus</i>, as a model, we found that Hco-ACR-26 and Hco-ACR-27 are co-expressed in body muscle cells. We demonstrated that co-expression of Hco-ACR-26 and Hco-ACR-27 in <i>Xenopus laevis</i> oocytes led to the functional expression of an acetylcholine-receptor highly sensitive to the anthelmintics morantel and pyrantel. Importantly we also reported that ACR-26 and ACR-27, from the distantly related parasitic nematode of horses, <i>Parascaris equorum</i>, also formed a functional acetylcholine-receptor highly sensitive to these two drugs. In <i>Caenorhabditis elegans</i>, a free-living model nematode, we demonstrated that heterologous expression of the <i>H</i>. <i>contortus</i> and <i>P</i>. <i>equorum</i> receptors drastically increased its sensitivity to morantel and pyrantel, mirroring the pharmacological properties observed in <i>Xenopus</i> oocytes. Our results are the first to describe significant molecular determinants of a novel class of nematode body wall muscle AChR.</p></div>", "links"=>[], "tags"=>["equorum receptors", "nematode body wall muscle AChR", "Caenorhabditis elegans", "Nematodes Acetylcholine receptors", "Xenopus laevis oocytes", "cholinergic agonist", "novel class", "acr", "heterologous expression", "gene family", "receptor subtypes", "anthelmintics morantel", "animal health", "antagonist anthelmintic drugs", "Xenopus oocytes", "body muscle cells", "Haemonchus contortus", "Functional Characterization", "Parascaris equorum"], "article_id"=>1615001, "categories"=>["Biological Sciences"], "users"=>["Elise Courtot", "Claude L. Charvet", "Robin N. Beech", "Abdallah Harmache", "Adrian J. Wolstenholme", "Lindy Holden-Dye", "Vincent O’Connor", "Nicolas Peineau", "Debra J. Woods", "Cedric Neveu"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1005267.s001", "https://dx.doi.org/10.1371/journal.ppat.1005267.s002", "https://dx.doi.org/10.1371/journal.ppat.1005267.s003", "https://dx.doi.org/10.1371/journal.ppat.1005267.s004", "https://dx.doi.org/10.1371/journal.ppat.1005267.s005", "https://dx.doi.org/10.1371/journal.ppat.1005267.s006", "https://dx.doi.org/10.1371/journal.ppat.1005267.s007", "https://dx.doi.org/10.1371/journal.ppat.1005267.s008"], "stats"=>{"downloads"=>47, "page_views"=>37, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Functional_Characterization_of_a_Novel_Class_of_Morantel_Sensitive_Acetylcholine_Receptors_in_Nematodes_/1615001", "title"=>"Functional Characterization of a Novel Class of Morantel-Sensitive Acetylcholine Receptors in Nematodes", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-12-01 02:49:51"}

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  • {"unique-ip"=>"6", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"36", "full-text"=>"37", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"14", "full-text"=>"18", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"18", "full-text"=>"22", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"15", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"7", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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