The Atypical Calpains: Evolutionary Analyses and Roles in Caenorhabditis elegans Cellular Degeneration
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{"title"=>"The atypical calpains: Evolutionary analyses and roles in Caenorhabditis elegans cellular degeneration", "type"=>"journal", "authors"=>[{"first_name"=>"Peter I.", "last_name"=>"Joyce", "scopus_author_id"=>"55162025400"}, {"first_name"=>"Rahul", "last_name"=>"Satija", "scopus_author_id"=>"15063431800"}, {"first_name"=>"Maozi", "last_name"=>"Chen", "scopus_author_id"=>"24450184700"}, {"first_name"=>"Patricia E.", "last_name"=>"Kuwabara", "scopus_author_id"=>"6701363143"}], "year"=>2012, "source"=>"PLoS Genetics", "identifiers"=>{"scopus"=>"2-s2.0-84859237505", "issn"=>"15537390", "pmid"=>"22479198", "isbn"=>"1553-7390", "doi"=>"10.1371/journal.pgen.1002602", "pui"=>"364556421", "sgr"=>"84859237505"}, "id"=>"db96f71a-d52f-3561-82c6-419fef737758", "abstract"=>"The calpains are physiologically important Ca(2+)-activated regulatory proteases, which are divided into typical or atypical sub-families based on constituent domains. Both sub-families are present in mammals, but our understanding of calpain function is based primarily on typical sub-family members. Here, we take advantage of the model organism Caenorhabditis elegans, which expresses only atypical calpains, to extend our knowledge of the phylogenetic evolution and function of calpains. We provide evidence that a typical human calpain protein with a penta EF hand, detected using custom profile hidden Markov models, is conserved in ancient metazoans and a divergent clade. These analyses also provide evidence for the lineage-specific loss of typical calpain genes in C. elegans and Ciona, and they reveal that many calpain-like genes lack an intact catalytic triad. Given the association between the dysregulation of typical calpains and human degenerative pathologies, we explored the phenotypes, expression profiles, and consequences of inappropriate reduction or activation of C. elegans atypical calpains. These studies show that the atypical calpain gene, clp-1, contributes to muscle degeneration and reveal that clp-1 activity is sensitive to genetic manipulation of [Ca(2+)](i). We show that CLP-1 localizes to sarcomeric sub-structures, but is excluded from dense bodies (Z-disks). We find that the muscle degeneration observed in a C. elegans model of dystrophin-based muscular dystrophy can be suppressed by clp-1 inactivation and that nemadipine-A inhibition of the EGL-19 calcium channel reveals that Ca(2+) dysfunction underlies the C. elegans MyoD model of myopathy. Taken together, our analyses highlight the roles of calcium dysregulation and CLP-1 in muscle myopathies and suggest that the atypical calpains could retain conserved roles in myofilament turnover.", "link"=>"http://www.mendeley.com/research/atypical-calpains-evolutionary-analyses-roles-caenorhabditis-elegans-cellular-degeneration", "reader_count"=>17, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>1, "Lecturer > Senior Lecturer"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>1, "Lecturer > Senior Lecturer"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>1, "Neuroscience"=>1, "Social Sciences"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>1}, "Social Sciences"=>{"Social Sciences"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}}, "reader_count_by_country"=>{"Sweden"=>1, "United States"=>1, "India"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/661345"], "description"=>"<p>(A) <i>pat-3p::gfp</i> integrin reporter (green) localizes to the M-lines, dense bodies and adhesion plaques. (B) <i>unc-54::clp-1::mrfp</i> (red) is expressed in sarcomeres and forms aggregates. (C) Co-localization of <i>unc-54::clp-1::mrfp</i> (red) (B) with the <i>pat-3p::gfp</i> integrin reporter (green) (A) at the M-line extending over the H-zone and adhesion plaques. <i>unc-54::clp-1::mrfp</i> does not co-localize at dense bodies. (D) <i>clp-1::gfp</i> shows a similar pattern of expression as (B), but is also expressed in neuronal structures marked with an asterisk. M-line, small arrowhead; H-zone, bracket; dense body (Z-disk), arrow; aggregates, open arrowhead; adhesion plaques, large arrowhead. Scale bar is 10 µm.</p>", "links"=>[], "tags"=>["localizes", "m-lines", "adhesions", "plaques"], "article_id"=>331828, "categories"=>["Biological Sciences", "Biochemistry", "Genetics", "Developmental Biology", "Evolutionary Biology"], "users"=>["Peter I. Joyce", "Rahul Satija", "Maozi Chen", "Patricia E. Kuwabara"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002602.g005", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ectopic_unc_54p_clp_1_mrfp_localizes_to_M_lines_and_adhesions_plaques_in_body_wall_muscle_/331828", "title"=>"Ectopic <i>unc-54p::clp-1::mrfp</i> localizes to M-lines and adhesions plaques in body wall muscle.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-29 00:30:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/661414"], "description"=>"<p>(A) Genetic mutations in calcium channel genes that are predicted to increase [Ca<sup>2+</sup>]<sub>i</sub> enhance <i>crIs4</i> [<i>unc-54p::clp-1</i>] induced paralysis. (B) DAPC mutants do not enhance <i>crIs4</i> [<i>unc-54p::clp-1</i>] induced paralysis unless combined with a mutation that also increases [Ca<sup>2+</sup>]<sub>i</sub>. Percentages represent the mean ± SEM from at least 4 independent experiments, which involved counting day 2 adults from synchronized worm populations (see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002602#s4\" target=\"_blank\">Materials and Methods</a>). For each experiment an n>120 was used, except for the strains <i>crIs4</i> and <i>dys-1(cx18); egl-19(ad695); crIs4</i> where an n>60 was used. In the absence of <i>crIs4</i>, none of the mutant genotypes led to paralysis (n>100, for each strain). <i>unc-24</i> mutants are Unc, but not paralyzed. Significance of difference by comparison to <i>crIs4</i> is based on Student's T-test (*, P<0.001) and (**, P = 0.043).</p>", "links"=>[], "tags"=>["enhancers", "induced"], "article_id"=>331902, "categories"=>["Biological Sciences", "Biochemistry", "Genetics", "Developmental Biology", "Evolutionary Biology"], "users"=>["Peter I. Joyce", "Rahul Satija", "Maozi Chen", "Patricia E. Kuwabara"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002602.g006", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Genetic_enhancers_of_crIs4_unc_54p_clp_1_induced_paralysis_/331902", "title"=>"Genetic enhancers of <i>crIs4</i> [<i>unc-54p::clp-1</i>] induced paralysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-29 00:31:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/661534"], "description"=>"a<p>Worms were grown at 15°C, and scored as Day 2 adults. Following phalloidin staining, the 20 most central muscle cells from each of the two most visible body wall muscle quadrants were scored (40 cells per animal), as described in Gieseler et al. (2000). Number represents the mean ± standard deviation from 3 independent experiments involving at least 30 animals per experiment.</p>b<p>Reduction is significantly different based from <i>dys-1(cx18); hlh-1(cc561ts)</i> based on Student's t-test (P<0.001).</p>", "links"=>[], "tags"=>["elegans", "suppresses", "dystrophin-based"], "article_id"=>332021, "categories"=>["Biological Sciences", "Biochemistry", "Genetics", "Developmental Biology", "Evolutionary Biology"], "users"=>["Peter I. Joyce", "Rahul Satija", "Maozi Chen", "Patricia E. Kuwabara"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002602.t002", "stats"=>{"downloads"=>11, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Deletion_of_C_elegans_clp_1_partially_suppresses_dystrophin_based_muscle_degeneration_/332021", "title"=>"Deletion of <i>C. elegans clp-1</i> partially suppresses dystrophin-based muscle degeneration.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-03-29 00:33:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/339215", "https://ndownloader.figshare.com/files/339266", "https://ndownloader.figshare.com/files/339402", "https://ndownloader.figshare.com/files/339444", "https://ndownloader.figshare.com/files/339466", "https://ndownloader.figshare.com/files/339513", "https://ndownloader.figshare.com/files/339546", "https://ndownloader.figshare.com/files/339587", "https://ndownloader.figshare.com/files/339619", "https://ndownloader.figshare.com/files/339653", "https://ndownloader.figshare.com/files/339687", "https://ndownloader.figshare.com/files/339725", "https://ndownloader.figshare.com/files/339781", "https://ndownloader.figshare.com/files/339846", "https://ndownloader.figshare.com/files/339904", "https://ndownloader.figshare.com/files/339968", "https://ndownloader.figshare.com/files/340116", "https://ndownloader.figshare.com/files/340154", "https://ndownloader.figshare.com/files/340195", "https://ndownloader.figshare.com/files/340249"], "description"=>"<div><p>The calpains are physiologically important Ca<sup>2+</sup>-activated regulatory proteases, which are divided into typical or atypical sub-families based on constituent domains. Both sub-families are present in mammals, but our understanding of calpain function is based primarily on typical sub-family members. Here, we take advantage of the model organism <em>Caenorhabditis elegans</em>, which expresses only atypical calpains, to extend our knowledge of the phylogenetic evolution and function of calpains. We provide evidence that a typical human calpain protein with a penta EF hand, detected using custom profile hidden Markov models, is conserved in ancient metazoans and a divergent clade. These analyses also provide evidence for the lineage-specific loss of typical calpain genes in <em>C. elegans</em> and Ciona, and they reveal that many calpain-like genes lack an intact catalytic triad. Given the association between the dysregulation of typical calpains and human degenerative pathologies, we explored the phenotypes, expression profiles, and consequences of inappropriate reduction or activation of <em>C. elegans</em> atypical calpains. These studies show that the atypical calpain gene, <em>clp-1</em>, contributes to muscle degeneration and reveal that <em>clp-1</em> activity is sensitive to genetic manipulation of [Ca<sup>2+</sup>]<sub>i</sub>. We show that CLP-1 localizes to sarcomeric sub-structures, but is excluded from dense bodies (Z-disks). We find that the muscle degeneration observed in a <em>C. elegans</em> model of dystrophin-based muscular dystrophy can be suppressed by <em>clp-1</em> inactivation and that nemadipine-A inhibition of the EGL-19 calcium channel reveals that Ca<sup>2+</sup> dysfunction underlies the <em>C. elegans</em> MyoD model of myopathy. Taken together, our analyses highlight the roles of calcium dysregulation and CLP-1 in muscle myopathies and suggest that the atypical calpains could retain conserved roles in myofilament turnover.</p> </div>", "links"=>[], "tags"=>["atypical", "evolutionary", "analyses", "roles", "cellular", "degeneration"], "article_id"=>127060, "categories"=>["Biological Sciences", "Biochemistry", "Genetics", "Developmental Biology", "Evolutionary Biology"], "users"=>["Peter I. Joyce", "Rahul Satija", "Maozi Chen", "Patricia E. Kuwabara"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002602.s001", "https://dx.doi.org/10.1371/journal.pgen.1002602.s002", "https://dx.doi.org/10.1371/journal.pgen.1002602.s003", "https://dx.doi.org/10.1371/journal.pgen.1002602.s004", "https://dx.doi.org/10.1371/journal.pgen.1002602.s005", "https://dx.doi.org/10.1371/journal.pgen.1002602.s006", "https://dx.doi.org/10.1371/journal.pgen.1002602.s007", "https://dx.doi.org/10.1371/journal.pgen.1002602.s008", "https://dx.doi.org/10.1371/journal.pgen.1002602.s009", "https://dx.doi.org/10.1371/journal.pgen.1002602.s010", "https://dx.doi.org/10.1371/journal.pgen.1002602.s011", "https://dx.doi.org/10.1371/journal.pgen.1002602.s012", "https://dx.doi.org/10.1371/journal.pgen.1002602.s013", "https://dx.doi.org/10.1371/journal.pgen.1002602.s014", "https://dx.doi.org/10.1371/journal.pgen.1002602.s015", "https://dx.doi.org/10.1371/journal.pgen.1002602.s016", "https://dx.doi.org/10.1371/journal.pgen.1002602.s017", "https://dx.doi.org/10.1371/journal.pgen.1002602.s018", "https://dx.doi.org/10.1371/journal.pgen.1002602.s019", "https://dx.doi.org/10.1371/journal.pgen.1002602.s020"], "stats"=>{"downloads"=>29, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_Atypical_Calpains_Evolutionary_Analyses_and_Roles_in_Caenorhabditis_elegans_Cellular_Degeneration/127060", "title"=>"The Atypical Calpains: Evolutionary Analyses and Roles in <em>Caenorhabditis elegans</em> Cellular Degeneration", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-03-29 01:57:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/661284"], "description"=>"<p>(A) Typical pattern of muscle striations in phenotypically wildtype <i>crIs4</i> adults. (B) Unc <i>crIs4</i> animal showing loss of actin striations (arrowhead). (C) Paralyzed <i>crIs4</i> animal with bundled muscle cells (dashed ring) and missing muscle cells (arrowhead). Scale bar, 10 µm.</p>", "links"=>[], "tags"=>["disrupts"], "article_id"=>331774, "categories"=>["Biological Sciences", "Biochemistry", "Genetics", "Developmental Biology", "Evolutionary Biology"], "users"=>["Peter I. Joyce", "Rahul Satija", "Maozi Chen", "Patricia E. Kuwabara"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002602.g004", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ectopic_crIs4_unc_54p_clp_1_expression_disrupts_body_wall_muscle_/331774", "title"=>"Ectopic <i>crIs4</i> [<i>unc-54p::clp-1</i>] expression disrupts body wall muscle.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-29 00:29:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/661113"], "description"=>"<p>(A) <i>clp-1p::nls-mrfp</i> (<i>crEx65</i>) is expressed in the ventral and dorsal (B) nerve cord. (C) <i>clp-4p::nls-mrfp</i> (<i>crEx74</i>) is expressed in the ventral and dorsal nerve cord. (D) <i>tra-3p::nls-mrfp</i> (<i>crEx78</i>) and (E) <i>clp-7p::nls-mrfp</i> (<i>crEx79</i>) are each expressed in the ventral nerve cord. Sites of co-localisation between <i>clp-1p::nls-mrfp</i>, <i>clp-4p::nls-mrfp</i>, <i>tra-3p::nls-mrfp</i> or <i>clp-7p::nls-mrfp</i> with <i>unc-119::gfp</i> expressed in ventral neuronal cell bodies are highlighted with white arrowheads; similarly, sites of co-localisation between <i>clp-1p::nls-mrfp</i> or <i>clp-4p::nls-mrfp</i> with <i>unc-119::gfp</i> expressed in dorsal neuronal cell bodies are highlighted with white arrows. Each micrograph is typical of the pattern observed with at least two other independent transgenic strains generated with the same reporter construct. <i>unc-119::gfp</i>, left (green); calpain promoter <i>nls</i>-<i>mrfp</i>, middle (red); and co-localization, right (yellow). Scale bar is 10 µM.</p>", "links"=>[], "tags"=>["pan-neuronal", "calpain", "transcriptional"], "article_id"=>331601, "categories"=>["Biological Sciences", "Biochemistry", "Genetics", "Developmental Biology", "Evolutionary Biology"], "users"=>["Peter I. Joyce", "Rahul Satija", "Maozi Chen", "Patricia E. Kuwabara"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002602.g002", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Co_localization_of_the_pan_neuronal_unc_119_gfp_reporter_with_calpain_nls_mrfp_transcriptional_reporters_/331601", "title"=>"Co-localization of the pan-neuronal <i>unc-119::gfp</i> reporter with calpain <i>nls</i>-<i>mrfp</i> transcriptional reporters.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-29 00:26:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/661205"], "description"=>"<p>Co-localization of the <i>myo-3p::gfp::nls</i> body wall muscle reporter with (A) <i>clp-1p::nls::mrfp</i> (<i>crEx65</i>) and (B) <i>clp-4p::mrfp</i> (<i>crEx74</i>). Co-localization of the <i>pes-6::gfp</i> excretory cell reporter with (C) <i>clp-4p::nls::mrfp</i> (<i>crEx74</i>), (D) <i>tra-3p::nls::mrfp</i> (<i>crEx78</i>) and (E) <i>clp-7p::nls::mrfp</i> (<i>crEx79</i>). (F) Co-localization of the <i>scm::gfp</i> seam cell reporter with <i>clp-7p::nls::mrfp</i> (<i>crEx79</i>). Tissue-specific GFP reporter, left (green), calpain promoter driven <i>nls::mrfp</i> expression, middle (red) and co-localization, right (yellow) highlighted with arrows. Each micrograph is typical of the pattern observed with at least two other independent transgenic strains generated with the same reporter construct. Scale bar, 10 µM.</p>", "links"=>[], "tags"=>["non-neuronal"], "article_id"=>331696, "categories"=>["Biological Sciences", "Biochemistry", "Genetics", "Developmental Biology", "Evolutionary Biology"], "users"=>["Peter I. Joyce", "Rahul Satija", "Maozi Chen", "Patricia E. Kuwabara"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002602.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Calpain_nls_mrfp_expression_in_non_neuronal_tissues_/331696", "title"=>"Calpain <i>nls::mrfp</i> expression in non-neuronal tissues.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-29 00:28:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/661567"], "description"=>"a<p>Body wall muscle.</p>b<p>Expression detected with both transcriptional and translational fusions.</p>c<p>Ventral nerve cord.</p>d<p>Dorsal nerve cord.</p>e<p>Expression is restricted to the intestine.</p>f<p>No expression detected throughout animal.</p>g<p>Absent in GABAergic neurons highlighted with <i>unc-47p</i>::<i>gfp</i> (EG1285).</p>h<p>Enhanced expression detected in pair of anterior-most intestinal nuclei.</p>", "links"=>[], "tags"=>["calpain", "transcriptional"], "article_id"=>332060, "categories"=>["Biological Sciences", "Biochemistry", "Genetics", "Developmental Biology", "Evolutionary Biology"], "users"=>["Peter I. Joyce", "Rahul Satija", "Maozi Chen", "Patricia E. Kuwabara"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002602.t001", "stats"=>{"downloads"=>5, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_C_elegans_calpain_transcriptional_reporter_expression_patterns_/332060", "title"=>"Summary of <i>C. elegans</i> calpain transcriptional reporter expression patterns.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-03-29 00:34:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/661015"], "description"=>"<p>Typical calpain EF hand motifs in DIV are highlighted; C-terminal EF hand motifs are absent in Nematoda and <i>Ciona intestinalis</i>. Other domains associated with calpain proteins include: PBH, PalB homology domain with some domain III homology; T/C2, C2 domain originally identified in TRA-3 <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002602#pgen.1002602-Barnes1\" target=\"_blank\">[33]</a>; Zn<sup>2+</sup>, zinc finger motif-containing; SolH, small optic lobes (SOL) homology domain; MIT 1, microtubule interacting and transport domain; and UCTH1, ubiquitin carboxyl-terminal hydrolase domain. The number of genes encoding proteins with the indicated modular arrangement of domains is indicated, left; the number of EF hands in DIV predicted by custom profile hidden Markov models are shown, right. Clades abbreviations: M, Metazoa; Pl, Placozoa; Eu, Eumetezoa; C, Cnidaria; B, Bilateria; P, Protostomia; D+Ch, Deuterostomia and Chordata; L, Lophotrochozoa; E, Ecdysozoa; N, Nematoda and A, Arthropoda. The tree is not drawn to scale. Protein accession numbers are available in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002602#s4\" target=\"_blank\">Materials and Methods</a>.</p>", "links"=>[], "tags"=>["analyses", "calpains", "metazoa", "lineage-specific"], "article_id"=>331498, "categories"=>["Biological Sciences", "Biochemistry", "Genetics", "Developmental Biology", "Evolutionary Biology"], "users"=>["Peter I. Joyce", "Rahul Satija", "Maozi Chen", "Patricia E. Kuwabara"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002602.g001", "stats"=>{"downloads"=>3, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Phylogenetic_analyses_of_typical_calpains_in_metazoa_support_a_model_of_lineage_specific_loss_/331498", "title"=>"Phylogenetic analyses of typical calpains in metazoa support a model of lineage-specific loss.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-29 00:24:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/661481"], "description"=>"<p>(A) Treatment with 5 µM nemadipine-A reduced <i>crIs4</i> [<i>unc-54p::clp-1</i>] induced paralysis in <i>egl-19</i>(<i>ad695</i>); <i>crIs4</i> and <i>hlh-1</i>(<i>cc561ts</i>); <i>crIs4</i> animals. % paralyzed animals for each strain are indicated with (+) or without (−) nemadipine-A treatment. Significance of difference based on Student's T-test compared to <i>egl-19</i>(<i>ad695</i>); <i>crIs4</i> (*, P<0.001) or <i>hlh-1</i>(<i>cc561ts</i>); <i>crIs4</i> (**, P = 0.001) without nemadipine-A treatment. (B) Treatment of <i>hlh-1</i>(<i>cc561ts</i>); <i>crIs4</i> animals with empty RNAi feeding vector (L4440), <i>clp-1</i>, or <i>asp-1</i> to <i>asp-6</i> (<i>RNAi</i>). Significance of difference compared to <i>hlh-1</i>(<i>cc561ts</i>); <i>crIs4</i> fed on empty vector (<i>RNAi</i>) is based on Student's T-test (*, P<0.001; **, P<0.05). Numbers shown represent the mean ± SEM from at least 5 independent experiments, which involved counting day 2 adults from synchronized worm populations (see Methods). n>60 per experiment.</p>", "links"=>[], "tags"=>["inhibition", "induced"], "article_id"=>331972, "categories"=>["Biological Sciences", "Biochemistry", "Genetics", "Developmental Biology", "Evolutionary Biology"], "users"=>["Peter I. Joyce", "Rahul Satija", "Maozi Chen", "Patricia E. Kuwabara"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002602.g007", "stats"=>{"downloads"=>2, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Small_molecule_and_genetic_inhibition_of_crIs4_unc_54p_clp_1_induced_paralysis_/331972", "title"=>"Small molecule and genetic inhibition of <i>crIs4</i> [<i>unc-54p::clp-1</i>] induced paralysis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-29 00:32:52"}

PMC Usage Stats | Further Information

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Relative Metric

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