Promotion of Bone Morphogenetic Protein Signaling by Tetraspanins and Glycosphingolipids
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{"title"=>"Promotion of Bone Morphogenetic Protein Signaling by Tetraspanins and Glycosphingolipids", "type"=>"journal", "authors"=>[{"first_name"=>"Zhiyu", "last_name"=>"Liu", "scopus_author_id"=>"55673620900"}, {"first_name"=>"Herong", "last_name"=>"Shi", "scopus_author_id"=>"23669142200"}, {"first_name"=>"Lindsey C.", "last_name"=>"Szymczak", "scopus_author_id"=>"56677667200"}, {"first_name"=>"Taner", "last_name"=>"Aydin", "scopus_author_id"=>"56677513000"}, {"first_name"=>"Sijung", "last_name"=>"Yun", "scopus_author_id"=>"56535844300"}, {"first_name"=>"Katharine", "last_name"=>"Constas", "scopus_author_id"=>"56677787800"}, {"first_name"=>"Arielle", "last_name"=>"Schaeffer", "scopus_author_id"=>"57198234929"}, {"first_name"=>"Sinthu", "last_name"=>"Ranjan", "scopus_author_id"=>"56677482200"}, {"first_name"=>"Saad", "last_name"=>"Kubba", "scopus_author_id"=>"56677651700"}, {"first_name"=>"Emad", "last_name"=>"Alam", "scopus_author_id"=>"56677610800"}, {"first_name"=>"Devin E.", "last_name"=>"McMahon", "scopus_author_id"=>"56677379200"}, {"first_name"=>"Jingpeng", "last_name"=>"He", "scopus_author_id"=>"56677029200"}, {"first_name"=>"Neta", "last_name"=>"Shwartz", "scopus_author_id"=>"56677590600"}, {"first_name"=>"Chenxi", "last_name"=>"Tian", "scopus_author_id"=>"36505373300"}, {"first_name"=>"Yevgeniy", "last_name"=>"Plavskin", "scopus_author_id"=>"57193967318"}, {"first_name"=>"Amanda", "last_name"=>"Lindy", "scopus_author_id"=>"57188738663"}, {"first_name"=>"Nimra Amir", "last_name"=>"Dad", "scopus_author_id"=>"56677684700"}, {"first_name"=>"Sunny", "last_name"=>"Sheth", "scopus_author_id"=>"56677393700"}, {"first_name"=>"Nirav M.", "last_name"=>"Amin", "scopus_author_id"=>"14324461300"}, {"first_name"=>"Stephanie", "last_name"=>"Zimmerman", "scopus_author_id"=>"55831397000"}, {"first_name"=>"Dennis", "last_name"=>"Liu", "scopus_author_id"=>"56676990900"}, {"first_name"=>"Erich M.", "last_name"=>"Schwarz", "scopus_author_id"=>"35412807400"}, {"first_name"=>"Harold", "last_name"=>"Smith", "scopus_author_id"=>"55192499500"}, {"first_name"=>"Michael W.", "last_name"=>"Krause", "scopus_author_id"=>"56497504600"}, {"first_name"=>"Jun", "last_name"=>"Liu", "scopus_author_id"=>"36071134500"}], "year"=>2015, "source"=>"PLoS Genetics", "identifiers"=>{"pui"=>"604818021", "sgr"=>"84930801520", "issn"=>"15537404", "pmid"=>"25978409", "scopus"=>"2-s2.0-84930801520", "doi"=>"10.1371/journal.pgen.1005221", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)"}, "id"=>"71b1edc8-01c5-3877-bff9-47263a394a85", "abstract"=>"Bone morphogenetic proteins (BMPs) belong to the transforming growth factor β (TGFβ) superfamily of secreted molecules. BMPs play essential roles in multiple developmental and homeostatic processes in metazoans. Malfunction of the BMP pathway can cause a variety of diseases in humans, including cancer, skeletal disorders and cardiovascular diseases. Identification of factors that ensure proper spatiotemporal control of BMP signaling is critical for understanding how this pathway is regulated. We have used a unique and sensitive genetic screen to identify the plasma membrane-localized tetraspanin TSP-21 as a key new factor in the C. elegans BMP-like \"Sma/Mab\" signaling pathway that controls body size and postembryonic M lineage development. We showed that TSP-21 acts in the signal-receiving cells and genetically functions at the ligand-receptor level. We further showed that TSP-21 can associate with itself and with two additional tetraspanins, TSP-12 and TSP-14, which also promote Sma/Mab signaling. TSP-12 and TSP-14 can also associate with SMA-6, the type I receptor of the Sma/Mab pathway. Finally, we found that glycosphingolipids, major components of the tetraspanin-enriched microdomains, are required for Sma/Mab signaling. Our findings suggest that the tetraspanin-enriched membrane microdomains are important for proper BMP signaling. As tetraspanins have emerged as diagnostic and prognostic markers for tumor progression, and TSP-21, TSP-12 and TSP-14 are all conserved in humans, we speculate that abnormal BMP signaling due to altered expression or function of certain tetraspanins may be a contributing factor to cancer development.", "link"=>"http://www.mendeley.com/research/promotion-bone-morphogenetic-protein-signaling-tetraspanins-glycosphingolipids", "reader_count"=>23, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Student > Doctoral Student"=>2, "Researcher"=>6, "Student > Ph. D. Student"=>12, "Student > Master"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Student > Doctoral Student"=>2, "Researcher"=>6, "Student > Ph. D. Student"=>12, "Student > Master"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>7, "Agricultural and Biological Sciences"=>9, "Medicine and Dentistry"=>3, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Unspecified"=>{"Unspecified"=>2}, "Environmental Science"=>{"Environmental Science"=>1}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2070533"], "description"=>"<p>Suppression was scored based on the re-appearance of M-derived CCs, which are missing in <i>sma-9(cc604)</i> mutant. All animals listed in this table are homozygous for <i>sma-9(cc604)</i> except in the case of <i>let-381(RNAi)</i>.</p><p>ND: not determined.</p><p><sup><i>a</i></sup> The worms scored are homozygous for <i>sma-9(cc604)</i> and homozygous for the mutation indicated.</p><p><sup><i>b</i></sup> The worms scored are homozygous for <i>sma-9(cc604)</i> and heterozygous for the mutation indicated.</p><p><sup><i>c</i></sup> Data from [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005221#pgen.1005221.ref020\" target=\"_blank\">20</a>]. All mutations are apparent null alleles.</p><p><sup><i>d</i></sup> Data from [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005221#pgen.1005221.ref021\" target=\"_blank\">21</a>]. <i>jj4</i> is an apparent null allele of <i>drag-1</i>.</p><p><sup><i>e</i></sup> Data from [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005221#pgen.1005221.ref022\" target=\"_blank\">22</a>]. <i>e1430</i> is an apparent null allele of <i>unc-40</i>.</p><p><sup><i>f</i></sup> The worms scored are wild-type worms or <i>sma-3(jj3)</i> worms treated with <i>let-381(RNAi)</i> post-embryonically (see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005221#sec015\" target=\"_blank\">Materials and methods</a>). <i>let-381(RNAi)</i> leads to the loss of M-derived CCs [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005221#pgen.1005221.ref033\" target=\"_blank\">33</a>].</p><p><sup><i>g</i></sup> The numbers shown refer to percentages of worms with 2 M-derived CCs, which likely resulted from inefficient <i>let-381(RNAi)</i>.</p><p>Mutations in known Sma/Mab pathway genes specifically suppress the <i>sma-9</i> M lineage phenotype.</p>", "links"=>[], "tags"=>["tumor progression", "spatiotemporal control", "Glycosphingolipids Bone", "prognostic markers", "cancer development", "Bone Morphogenetic Protein Signaling", "sma", "growth factor β", "postembryonic M lineage development", "BMP pathway", "tetraspanin", "controls body size", "homeostatic processes", "tgf", "tsp"], "article_id"=>1417024, "categories"=>["Biological Sciences"], "users"=>["Zhiyu Liu", "Herong Shi", "Lindsey C. Szymczak", "Taner Aydin", "Sijung Yun", "Katharine Constas", "Arielle Schaeffer", "Sinthu Ranjan", "Saad Kubba", "Emad Alam", "Devin E. McMahon", "Jingpeng He", "Neta Shwartz", "Chenxi Tian", "Yevgeniy Plavskin", "Amanda Lindy", "Nimra Amir Dad", "Sunny Sheth", "Nirav M. Amin", "Stephanie Zimmerman", "Dennis Liu", "Erich M. Schwarz", "Harold Smith", "Michael W. Krause", "Jun Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005221.t001", "stats"=>{"downloads"=>6, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mutations_in_known_Sma_Mab_pathway_genes_specifically_suppress_the_sma_9_M_lineage_phenotype_/1417024", "title"=>"Mutations in known Sma/Mab pathway genes specifically suppress the <i>sma-9</i> M lineage phenotype.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-05-15 03:35:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/2070535"], "description"=>"<p>Suppression was determined based on the number of M lineage-derived coelomocytes (CCs). <i>sma-9(cc604)</i> hermaphrodites have 0 M lineage-derived CCs, while wild-type worms have 2.</p><p>ND: not determined</p><p><sup>a</sup> The worms scored are homozygous for <i>sma-9(cc604)</i> and homozygous for the suppressor indicated.</p><p><sup>b</sup> The worms scored are homozygous for <i>sma-9(cc604)</i> and heterozygous for the suppressor indicated.</p><p><sup>c</sup> Reported in [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005221#pgen.1005221.ref020\" target=\"_blank\">20</a>].</p><p><sup>d</sup> Reported in [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005221#pgen.1005221.ref021\" target=\"_blank\">21</a>].</p><p><sup>e</sup> Reported in [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005221#pgen.1005221.ref022\" target=\"_blank\">22</a>].</p><p><sup>f</sup> Both <i>jj65</i> and <i>jj85</i> complemented <i>dbl-1(wk70)</i> and do not carry any molecular lesions in the <i>dbl-1</i> coding or 5’ and 3’ regulatory regions.</p><p><sup>g</sup><i>jj58</i> might be a dominant <i>sma-9</i> suppressor and was not characterized in this study.</p><p><sup>h</sup><i>jj68</i>, <i>jj80</i>, <i>jj81</i> and <i>jj84</i> were not characterized in this study due to their low degree of suppression of the <i>sma-9</i> M lineage phenotype.</p><p><sup>i</sup> Predicted based on likely splicing defect.</p><p><sup>j</sup> The predicted truncation at the amino acid level was calculated assuming that the large deletion does not affect the stability of the <i>lon-2</i> message in <i>jj61</i> animals. The deletion also deletes the majority of the <i>aman-1</i> coding region, leaving only 338bp of the <i>aman-1</i> first exon to be present. The Susm phenotype is due to the loss of <i>lon-2</i> function because <i>jj61</i> failed to complement <i>lon-2(e678)</i> for the Susm phenotype.</p><p><sup>k</sup> Aberrant transcripts were confirmed by RT-PCR and reported in [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005221#pgen.1005221.ref022\" target=\"_blank\">22</a>].</p><p><sup>l</sup> Corresponding genes were identified via a combination of linkage analysis (linkage to <i>cup-5(ar465)</i> III, <i>sma-9(cc604) X</i>), snip-SNP mapping [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005221#pgen.1005221.ref086\" target=\"_blank\">86</a>], and complementation tests based on the Susm phenotype, with the following alleles: <i>dbl-1(wk70)</i>, <i>sma-6(e1482)</i>, <i>daf-4(m63)</i>, <i>sma-2(e502)</i>, <i>sma-3(e491)</i>, <i>sma-4(e729)</i>, <i>lon-2(e678)</i>, and <i>lon-1(e185)</i>.</p><p><sup>m</sup> Corresponding genes were identified via WGS (see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005221#sec015\" target=\"_blank\">Materials and methods</a>).</p><p><sup>n</sup> Corresponding genes were identified via SNP-WGS (see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005221#sec015\" target=\"_blank\">Materials and methods</a>).</p><p><sup>o</sup> In addition to carrying a mutation in <i>sma-4</i>, <i>jj70</i> appears to carry another <i>sma-9</i> suppressing mutation that maps to LG V and fails to complement <i>jj65</i> and <i>jj85</i>.</p><p><sup>p</sup> All molecular lesions were identified or confirmed by Sanger Sequencing.</p><p><sup>q</sup> A fragment containing 3kb of upstream sequences, the genomic coding region and 2kb of downstream sequences of <i>sma-6</i> rescued the Susm phenotype of <i>jj69</i>.</p><p>Summary of the mutant alleles isolated in the <i>sma-9</i> suppressor screen.</p>", "links"=>[], "tags"=>["tumor progression", "spatiotemporal control", "Glycosphingolipids Bone", "prognostic markers", "cancer development", "Bone Morphogenetic Protein Signaling", "sma", "growth factor β", "postembryonic M lineage development", "BMP pathway", "tetraspanin", "controls body size", "homeostatic processes", "tgf", "tsp"], "article_id"=>1417026, "categories"=>["Biological Sciences"], "users"=>["Zhiyu Liu", "Herong Shi", "Lindsey C. Szymczak", "Taner Aydin", "Sijung Yun", "Katharine Constas", "Arielle Schaeffer", "Sinthu Ranjan", "Saad Kubba", "Emad Alam", "Devin E. McMahon", "Jingpeng He", "Neta Shwartz", "Chenxi Tian", "Yevgeniy Plavskin", "Amanda Lindy", "Nimra Amir Dad", "Sunny Sheth", "Nirav M. Amin", "Stephanie Zimmerman", "Dennis Liu", "Erich M. Schwarz", "Harold Smith", "Michael W. Krause", "Jun Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005221.t002", "stats"=>{"downloads"=>4, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_the_mutant_alleles_isolated_in_the_sma_9_suppressor_screen_/1417026", "title"=>"Summary of the mutant alleles isolated in the <i>sma-9</i> suppressor screen.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-05-15 03:35:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/2070536"], "description"=>"<p>Suppression of the <i>sma-9(0)</i> M lineage defects by <i>tsp-21</i> mutations.</p>", "links"=>[], "tags"=>["tumor progression", "spatiotemporal control", "Glycosphingolipids Bone", "prognostic markers", "cancer development", "Bone Morphogenetic Protein Signaling", "sma", "growth factor β", "postembryonic M lineage development", "BMP pathway", "tetraspanin", "controls body size", "homeostatic processes", "tgf", "tsp"], "article_id"=>1417027, "categories"=>["Biological Sciences"], "users"=>["Zhiyu Liu", "Herong Shi", "Lindsey C. Szymczak", "Taner Aydin", "Sijung Yun", "Katharine Constas", "Arielle Schaeffer", "Sinthu Ranjan", "Saad Kubba", "Emad Alam", "Devin E. McMahon", "Jingpeng He", "Neta Shwartz", "Chenxi Tian", "Yevgeniy Plavskin", "Amanda Lindy", "Nimra Amir Dad", "Sunny Sheth", "Nirav M. Amin", "Stephanie Zimmerman", "Dennis Liu", "Erich M. Schwarz", "Harold Smith", "Michael W. Krause", "Jun Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005221.t003", "stats"=>{"downloads"=>10, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Suppression_of_the_sma_9_0_M_lineage_defects_by_tsp_21_mutations_/1417027", "title"=>"Suppression of the <i>sma-9(0)</i> M lineage defects by <i>tsp-21</i> mutations.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-05-15 03:35:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/2070537"], "description"=>"<p>Body length was normalized to that of <i>tsp-21(jj77)</i> mutants. For each genotype, data from two transgenic lines were pooled and averaged. Data shown are mean ± s.e.m.</p><p>***<i>p</i><0.0001, different transgenic worms versus <i>tsp-21(jj77)</i> (unpaired two-tailed Student’s <i>t</i>-test).</p><p>Rescue of the small body size of <i>tsp-21(jj77)</i> worms by tissue-specific expression of <i>tsp-21</i> cDNA.</p>", "links"=>[], "tags"=>["tumor progression", "spatiotemporal control", "Glycosphingolipids Bone", "prognostic markers", "cancer development", "Bone Morphogenetic Protein Signaling", "sma", "growth factor β", "postembryonic M lineage development", "BMP pathway", "tetraspanin", "controls body size", "homeostatic processes", "tgf", "tsp"], "article_id"=>1417028, "categories"=>["Biological Sciences"], "users"=>["Zhiyu Liu", "Herong Shi", "Lindsey C. Szymczak", "Taner Aydin", "Sijung Yun", "Katharine Constas", "Arielle Schaeffer", "Sinthu Ranjan", "Saad Kubba", "Emad Alam", "Devin E. McMahon", "Jingpeng He", "Neta Shwartz", "Chenxi Tian", "Yevgeniy Plavskin", "Amanda Lindy", "Nimra Amir Dad", "Sunny Sheth", "Nirav M. Amin", "Stephanie Zimmerman", "Dennis Liu", "Erich M. Schwarz", "Harold Smith", "Michael W. Krause", "Jun Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005221.t004", "stats"=>{"downloads"=>4, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rescue_of_the_small_body_size_of_tsp_21_jj77_worms_by_tissue_specific_expression_of_tsp_21_cDNA_/1417028", "title"=>"Rescue of the small body size of <i>tsp-21(jj77)</i> worms by tissue-specific expression of <i>tsp-21</i> cDNA.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-05-15 03:35:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/2070538"], "description"=>"<p><i>tsp-21(RNAi)</i> was used as a positive control for the <i>sma-9</i> suppression assay.</p><p>RNAi of other <i>tsp</i> genes (<i>tsp-1</i>, <i>2</i>, <i>3</i>, <i>4</i>, <i>5</i>, <i>6</i>, <i>7</i>, <i>8</i>, <i>9</i>, <i>10</i>, <i>11</i>, <i>13</i>, <i>16</i>, <i>17</i>, <i>18</i>, <i>19</i>, <i>20</i>) gave similar results as <i>tsp-10(RNAi)</i>, while <i>tsp-15(RNAi)</i> resulted in embryonic/larval lethality, consistent with previous reports on <i>tsp-15</i> function [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005221#pgen.1005221.ref105\" target=\"_blank\">105</a>].</p><p>***<i>p</i><0.0001 (unpaired two-tailed Student’s <i>t</i>-test)</p><p><sup>a</sup><i>tsp; sma-9(cc604)</i> double mutants vs. <i>sma-9(cc604)</i> single mutants.</p><p><sup>b</sup><i>tsp-12(ok239); tsp-14(RNAi) sma-9(cc604)</i> mutants vs. <i>tsp-12(ok239); sma-9(cc604)</i> mutants.</p><p>TSP-12 and TSP-14 function redundantly to promote Sma/Mab signaling.</p>", "links"=>[], "tags"=>["tumor progression", "spatiotemporal control", "Glycosphingolipids Bone", "prognostic markers", "cancer development", "Bone Morphogenetic Protein Signaling", "sma", "growth factor β", "postembryonic M lineage development", "BMP pathway", "tetraspanin", "controls body size", "homeostatic processes", "tgf", "tsp"], "article_id"=>1417029, "categories"=>["Biological Sciences"], "users"=>["Zhiyu Liu", "Herong Shi", "Lindsey C. Szymczak", "Taner Aydin", "Sijung Yun", "Katharine Constas", "Arielle Schaeffer", "Sinthu Ranjan", "Saad Kubba", "Emad Alam", "Devin E. McMahon", "Jingpeng He", "Neta Shwartz", "Chenxi Tian", "Yevgeniy Plavskin", "Amanda Lindy", "Nimra Amir Dad", "Sunny Sheth", "Nirav M. Amin", "Stephanie Zimmerman", "Dennis Liu", "Erich M. Schwarz", "Harold Smith", "Michael W. Krause", "Jun Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005221.t005", "stats"=>{"downloads"=>7, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TSP_12_and_TSP_14_function_redundantly_to_promote_Sma_Mab_signaling_/1417029", "title"=>"TSP-12 and TSP-14 function redundantly to promote Sma/Mab signaling.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-05-15 03:35:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/2070540"], "description"=>"<p>***<i>p</i><0.001, <i>lin-12(n676n930ts); tsp-21(jj77)</i> versus <i>lin-12(n676n930ts)</i> worms (unpaired two-tailed Student’s <i>t</i>-test).</p><p>TSP-21 positively modulates LIN-12/Notch signaling in the M lineage.</p>", "links"=>[], "tags"=>["tumor progression", "spatiotemporal control", "Glycosphingolipids Bone", "prognostic markers", "cancer development", "Bone Morphogenetic Protein Signaling", "sma", "growth factor β", "postembryonic M lineage development", "BMP pathway", "tetraspanin", "controls body size", "homeostatic processes", "tgf", "tsp"], "article_id"=>1417031, "categories"=>["Biological Sciences"], "users"=>["Zhiyu Liu", "Herong Shi", "Lindsey C. Szymczak", "Taner Aydin", "Sijung Yun", "Katharine Constas", "Arielle Schaeffer", "Sinthu Ranjan", "Saad Kubba", "Emad Alam", "Devin E. McMahon", "Jingpeng He", "Neta Shwartz", "Chenxi Tian", "Yevgeniy Plavskin", "Amanda Lindy", "Nimra Amir Dad", "Sunny Sheth", "Nirav M. Amin", "Stephanie Zimmerman", "Dennis Liu", "Erich M. Schwarz", "Harold Smith", "Michael W. Krause", "Jun Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005221.t006", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TSP_21_positively_modulates_LIN_12_Notch_signaling_in_the_M_lineage_/1417031", "title"=>"TSP-21 positively modulates LIN-12/Notch signaling in the M lineage.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-05-15 03:35:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/2070542"], "description"=>"<p>Animals were growing at 20°C and scored at the L4 stage except for <i>cgt-3(ok2877)</i>* animals, which were arrested at late L1/early L2, and for the cold-sensitive <i>pod-2(ye60)</i>** animals which were growing at 15°C during postembryonic development.</p><p>***<i>p</i><0.0001, <i>cgt-3(ok2877); jjEx[hlh-8p</i>::<i>cgt-3]</i> versus <i>cgt-3(ok2877)</i> worms (unpaired two-tailed Student’s <i>t</i>-test).</p><p><sup>a</sup> The <i>sma-9</i> gene product is not listed in this column.</p><p><sup>b</sup> Data generated by averaging the results from three independent transgenic lines.</p><p>Mutations in enzymes critical for glycosphigolipid (GSL) biosynthesis are defective in Sma/Mab signaling.</p>", "links"=>[], "tags"=>["tumor progression", "spatiotemporal control", "Glycosphingolipids Bone", "prognostic markers", "cancer development", "Bone Morphogenetic Protein Signaling", "sma", "growth factor β", "postembryonic M lineage development", "BMP pathway", "tetraspanin", "controls body size", "homeostatic processes", "tgf", "tsp"], "article_id"=>1417033, "categories"=>["Biological Sciences"], "users"=>["Zhiyu Liu", "Herong Shi", "Lindsey C. Szymczak", "Taner Aydin", "Sijung Yun", "Katharine Constas", "Arielle Schaeffer", "Sinthu Ranjan", "Saad Kubba", "Emad Alam", "Devin E. McMahon", "Jingpeng He", "Neta Shwartz", "Chenxi Tian", "Yevgeniy Plavskin", "Amanda Lindy", "Nimra Amir Dad", "Sunny Sheth", "Nirav M. Amin", "Stephanie Zimmerman", "Dennis Liu", "Erich M. Schwarz", "Harold Smith", "Michael W. Krause", "Jun Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005221.t007", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mutations_in_enzymes_critical_for_glycosphigolipid_GSL_biosynthesis_are_defective_in_Sma_Mab_signaling_/1417033", "title"=>"Mutations in enzymes critical for glycosphigolipid (GSL) biosynthesis are defective in Sma/Mab signaling.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-05-15 03:35:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/2070543"], "description"=>"<p><i>cgt-3</i> and <i>bre-5</i> mutants exhibit defects in LIN-12/Notch signaling in the M lineage.</p>", "links"=>[], "tags"=>["tumor progression", "spatiotemporal control", "Glycosphingolipids Bone", "prognostic markers", "cancer development", "Bone Morphogenetic Protein Signaling", "sma", "growth factor β", "postembryonic M lineage development", "BMP pathway", "tetraspanin", "controls body size", "homeostatic processes", "tgf", "tsp"], "article_id"=>1417034, "categories"=>["Biological Sciences"], "users"=>["Zhiyu Liu", "Herong Shi", "Lindsey C. Szymczak", "Taner Aydin", "Sijung Yun", "Katharine Constas", "Arielle Schaeffer", "Sinthu Ranjan", "Saad Kubba", "Emad Alam", "Devin E. McMahon", "Jingpeng He", "Neta Shwartz", "Chenxi Tian", "Yevgeniy Plavskin", "Amanda Lindy", "Nimra Amir Dad", "Sunny Sheth", "Nirav M. Amin", "Stephanie Zimmerman", "Dennis Liu", "Erich M. Schwarz", "Harold Smith", "Michael W. Krause", "Jun Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005221.t008", "stats"=>{"downloads"=>5, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_cgt_3_and_bre_5_mutants_exhibit_defects_in_LIN_12_Notch_signaling_in_the_M_lineage_/1417034", "title"=>"<i>cgt-3</i> and <i>bre-5</i> mutants exhibit defects in LIN-12/Notch signaling in the M lineage.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-05-15 03:35:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/2070550", "https://ndownloader.figshare.com/files/2070551", "https://ndownloader.figshare.com/files/2070552", "https://ndownloader.figshare.com/files/2070553", "https://ndownloader.figshare.com/files/2070554", "https://ndownloader.figshare.com/files/2070555", "https://ndownloader.figshare.com/files/2070556"], "description"=>"<div><p>Bone morphogenetic proteins (BMPs) belong to the transforming growth factor β (TGFβ) superfamily of secreted molecules. BMPs play essential roles in multiple developmental and homeostatic processes in metazoans. Malfunction of the BMP pathway can cause a variety of diseases in humans, including cancer, skeletal disorders and cardiovascular diseases. Identification of factors that ensure proper spatiotemporal control of BMP signaling is critical for understanding how this pathway is regulated. We have used a unique and sensitive genetic screen to identify the plasma membrane-localized tetraspanin TSP-21 as a key new factor in the <i>C</i>. <i>elegans</i> BMP-like “Sma/Mab” signaling pathway that controls body size and postembryonic M lineage development. We showed that TSP-21 acts in the signal-receiving cells and genetically functions at the ligand-receptor level. We further showed that TSP-21 can associate with itself and with two additional tetraspanins, TSP-12 and TSP-14, which also promote Sma/Mab signaling. TSP-12 and TSP-14 can also associate with SMA-6, the type I receptor of the Sma/Mab pathway. Finally, we found that glycosphingolipids, major components of the tetraspanin-enriched microdomains, are required for Sma/Mab signaling. Our findings suggest that the tetraspanin-enriched membrane microdomains are important for proper BMP signaling. As tetraspanins have emerged as diagnostic and prognostic markers for tumor progression, and TSP-21, TSP-12 and TSP-14 are all conserved in humans, we speculate that abnormal BMP signaling due to altered expression or function of certain tetraspanins may be a contributing factor to cancer development.</p></div>", "links"=>[], "tags"=>["tumor progression", "spatiotemporal control", "Glycosphingolipids Bone", "prognostic markers", "cancer development", "Bone Morphogenetic Protein Signaling", "sma", "growth factor β", "postembryonic M lineage development", "BMP pathway", "tetraspanin", "controls body size", "homeostatic processes", "tgf", "tsp"], "article_id"=>1417041, "categories"=>["Biological Sciences"], "users"=>["Zhiyu Liu", "Herong Shi", "Lindsey C. Szymczak", "Taner Aydin", "Sijung Yun", "Katharine Constas", "Arielle Schaeffer", "Sinthu Ranjan", "Saad Kubba", "Emad Alam", "Devin E. McMahon", "Jingpeng He", "Neta Shwartz", "Chenxi Tian", "Yevgeniy Plavskin", "Amanda Lindy", "Nimra Amir Dad", "Sunny Sheth", "Nirav M. Amin", "Stephanie Zimmerman", "Dennis Liu", "Erich M. Schwarz", "Harold Smith", "Michael W. Krause", "Jun Liu"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1005221.s001", "https://dx.doi.org/10.1371/journal.pgen.1005221.s002", "https://dx.doi.org/10.1371/journal.pgen.1005221.s003", "https://dx.doi.org/10.1371/journal.pgen.1005221.s004", "https://dx.doi.org/10.1371/journal.pgen.1005221.s005", "https://dx.doi.org/10.1371/journal.pgen.1005221.s006", "https://dx.doi.org/10.1371/journal.pgen.1005221.s007"], "stats"=>{"downloads"=>22, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Promotion_of_Bone_Morphogenetic_Protein_Signaling_by_Tetraspanins_and_Glycosphingolipids_/1417041", "title"=>"Promotion of Bone Morphogenetic Protein Signaling by Tetraspanins and Glycosphingolipids", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-05-15 03:35:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/2070506"], "description"=>"<p>(A, B) Schematic representation of the M lineage in wild-type or <i>sma-9(0);susm</i> (A), and <i>sma-9(0)</i> (B) animals. (C-D) Diagrams of an adult wild-type or <i>sma-9(0);susm</i> worm (C) and an adult <i>sma-9(0)</i> animal (D), showing the CC phenotype. <i>sma-9(0)</i> mutants lack the two M-derived CC that are present in wild-type or <i>sma-9(0);susm</i> animals (in blue arrowheads). (E and F) Merged GFP and DIC images of <i>tsp-21(jj77) sma-9(cc604)</i> (E) and <i>sma-9(cc604)</i> (F) worms carrying the <i>CC</i>::<i>gfp</i> marker at the late L4 stage. BWM: body-wall muscle, CC: coelomocyte, SM: sex myoblast. d: dorsal, v: ventral, l: left, r: right, a: anterior, p: posterior.</p>", "links"=>[], "tags"=>["tumor progression", "spatiotemporal control", "Glycosphingolipids Bone", "prognostic markers", "cancer development", "Bone Morphogenetic Protein Signaling", "sma", "growth factor β", "postembryonic M lineage development", "BMP pathway", "tetraspanin", "controls body size", "homeostatic processes", "tgf", "tsp"], "article_id"=>1416998, "categories"=>["Biological Sciences"], "users"=>["Zhiyu Liu", "Herong Shi", "Lindsey C. Szymczak", "Taner Aydin", "Sijung Yun", "Katharine Constas", "Arielle Schaeffer", "Sinthu Ranjan", "Saad Kubba", "Emad Alam", "Devin E. McMahon", "Jingpeng He", "Neta Shwartz", "Chenxi Tian", "Yevgeniy Plavskin", "Amanda Lindy", "Nimra Amir Dad", "Sunny Sheth", "Nirav M. Amin", "Stephanie Zimmerman", "Dennis Liu", "Erich M. Schwarz", "Harold Smith", "Michael W. Krause", "Jun Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005221.g001", "stats"=>{"downloads"=>1, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_sma_9_0_suppressor_mutations_revert_the_M_lineage_dorsal_to_ventral_fate_transformation_defect_in_sma_9_0_mutants_to_the_wild_type_pattern_/1416998", "title"=>"The <i>sma-9(0)</i> suppressor mutations revert the M lineage dorsal-to-ventral fate transformation defect in <i>sma-9(0)</i> mutants to the wild-type pattern.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-15 03:35:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/2070509"], "description"=>"<p>(A) The Sma/Mab pathway, showing the core pathway members (DBL-1, SMA-6, DAF-4, SMA-2, 3 and 4) as well as the previously identified positive (SMA-10, DRAG-1 and UNC-40) and negative (LON-2) modulators. We propose that LON-1 also negatively regulates Sma/Mab signaling via a feedback mechanism (dashed line). (B-D) DIC images showing the body size of wild type (B), <i>tsp-21(jj77)</i> (C) and <i>dbl-1(wk70)</i> (D) worms at the Christmas tree stage of vulval development. (E) Relative body lengths of stage-matched wild-type and various mutant worms measured at the Christmas tree stage. *** <i>p</i><0.0001, (unpaired two-tailed Student’s <i>t</i>-test). Error bars represent 95% confidence intervals for the normalized body length. ND, not different.</p>", "links"=>[], "tags"=>["tumor progression", "spatiotemporal control", "Glycosphingolipids Bone", "prognostic markers", "cancer development", "Bone Morphogenetic Protein Signaling", "sma", "growth factor β", "postembryonic M lineage development", "BMP pathway", "tetraspanin", "controls body size", "homeostatic processes", "tgf", "tsp"], "article_id"=>1417001, "categories"=>["Biological Sciences"], "users"=>["Zhiyu Liu", "Herong Shi", "Lindsey C. Szymczak", "Taner Aydin", "Sijung Yun", "Katharine Constas", "Arielle Schaeffer", "Sinthu Ranjan", "Saad Kubba", "Emad Alam", "Devin E. McMahon", "Jingpeng He", "Neta Shwartz", "Chenxi Tian", "Yevgeniy Plavskin", "Amanda Lindy", "Nimra Amir Dad", "Sunny Sheth", "Nirav M. Amin", "Stephanie Zimmerman", "Dennis Liu", "Erich M. Schwarz", "Harold Smith", "Michael W. Krause", "Jun Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005221.g002", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TSP_21_functions_at_the_ligand_receptor_level_to_positively_modulate_Sma_Mab_signaling_/1417001", "title"=>"TSP-21 functions at the ligand-receptor level to positively modulate Sma/Mab signaling.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-15 03:35:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/2070511"], "description"=>"<p>(A-H) Hypodermal expression of the RAD-SMAD GFP reporter in wild type (A, E), <i>dbl-1(wk70)</i> (B, F), <i>lon-2(e678)</i> (C, G) and <i>tsp-21(jj77)</i> (D, H) worms at the L2 stage. The exposure time for all the GFP images was identical. (I) Quantification of the hypodermal RAD-SMAD GFP fluorescence intensity in various mutants compared with wild-type animals (set to 1). *** <i>p</i><0.0001, (unpaired two-tailed Student’s <i>t</i>-test). Error bars represent 95% confidence intervals for the normalized RAD-SMAD intensity.</p>", "links"=>[], "tags"=>["tumor progression", "spatiotemporal control", "Glycosphingolipids Bone", "prognostic markers", "cancer development", "Bone Morphogenetic Protein Signaling", "sma", "growth factor β", "postembryonic M lineage development", "BMP pathway", "tetraspanin", "controls body size", "homeostatic processes", "tgf", "tsp"], "article_id"=>1417003, "categories"=>["Biological Sciences"], "users"=>["Zhiyu Liu", "Herong Shi", "Lindsey C. Szymczak", "Taner Aydin", "Sijung Yun", "Katharine Constas", "Arielle Schaeffer", "Sinthu Ranjan", "Saad Kubba", "Emad Alam", "Devin E. McMahon", "Jingpeng He", "Neta Shwartz", "Chenxi Tian", "Yevgeniy Plavskin", "Amanda Lindy", "Nimra Amir Dad", "Sunny Sheth", "Nirav M. Amin", "Stephanie Zimmerman", "Dennis Liu", "Erich M. Schwarz", "Harold Smith", "Michael W. Krause", "Jun Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005221.g003", "stats"=>{"downloads"=>2, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_tsp_21_jj77_mutants_exhibit_reduced_RAD_SMAD_reporter_expression_/1417003", "title"=>"<i>tsp-21(jj77)</i> mutants exhibit reduced RAD-SMAD reporter expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-15 03:35:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/2070517"], "description"=>"<p>(A) A schematic of the TSP-21 protein, showing the four transmembrane (TM) domains and the two extracellular loops (EC1 and EC2). The locations of the <i>jj60</i> and <i>jj77</i> molecular lesions are shown. (B) Diagrams of the <i>tsp-21</i> genomic and GFP tagged constructs. The location of the <i>tm6269</i> deletion as well as the <i>jj60</i> and <i>jj77</i> molecular lesions are shown. (C) A ClustalX sequence alignment [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005221#pgen.1005221.ref104\" target=\"_blank\">104</a>] of TSP-21 and other C6a tetraspanins from <i>Drosophila</i>, human and mouse, highlighting the four transmembrane domains (shaded light green), the conserved cysteine residues (red letters) and the amino acids mutated or deleted in <i>jj60</i> or <i>jj77</i> (red boxes). Identical residues are marked with asterisks (*) and conserved residues are marked with either colons (:) or periods (.) above the alignment. The Genbank accession numbers for the proteins shown in panel C are: <i>Drosophila</i> Tsp5D (isoform C, NP_001259266.1), human TSPAN4 (NP_001020406.1), mouse Tspan-4 (NP_001239517.1), human TSPAN9 (NP_001161792.1), mouse Tspan-9 (NP_780623.1).</p>", "links"=>[], "tags"=>["tumor progression", "spatiotemporal control", "Glycosphingolipids Bone", "prognostic markers", "cancer development", "Bone Morphogenetic Protein Signaling", "sma", "growth factor β", "postembryonic M lineage development", "BMP pathway", "tetraspanin", "controls body size", "homeostatic processes", "tgf", "tsp"], "article_id"=>1417008, "categories"=>["Biological Sciences"], "users"=>["Zhiyu Liu", "Herong Shi", "Lindsey C. Szymczak", "Taner Aydin", "Sijung Yun", "Katharine Constas", "Arielle Schaeffer", "Sinthu Ranjan", "Saad Kubba", "Emad Alam", "Devin E. McMahon", "Jingpeng He", "Neta Shwartz", "Chenxi Tian", "Yevgeniy Plavskin", "Amanda Lindy", "Nimra Amir Dad", "Sunny Sheth", "Nirav M. Amin", "Stephanie Zimmerman", "Dennis Liu", "Erich M. Schwarz", "Harold Smith", "Michael W. Krause", "Jun Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005221.g004", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_tsp_21_encodes_a_conserved_tetraspanin_protein_of_the_C6a_group_/1417008", "title"=>"<i>tsp-21</i> encodes a conserved tetraspanin protein of the C6a group.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-15 03:35:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/2070527"], "description"=>"<p>(A-R) Mid-stage embryo (A-C) or L1 larvae (D-L) or L4 larvae (M-R) showing confocal images of TSP-21::GFP (A, D, G, J, M, P), the corresponding DIC (B, E, H, K, N, Q) and merged images (C, F, I, L, O, R). TSP-21::GFP is localized to the plasma membrane of hypodermal and pharyngeal cells in embryos (A-C), pharyngeal cells (D-F), intestinal cells (G-I) and hypodermal cells (J-L) in L1 larvae, the developing gonad (M-O) and rectal epithelium (P-R) in L4 larvae. (S-Z) L1 larvae expressing both TSP-21::GFP and the M lineage specific reporter <i>hlh-8p</i>::<i>nls</i>::<i>rfp</i>. TSP-21::GFP is present in the M lineage from the 1-M stage through the 16-M stage. Some M lineage cells are out of the focal plane and not shown in panels U-V and Y-Z.</p>", "links"=>[], "tags"=>["tumor progression", "spatiotemporal control", "Glycosphingolipids Bone", "prognostic markers", "cancer development", "Bone Morphogenetic Protein Signaling", "sma", "growth factor β", "postembryonic M lineage development", "BMP pathway", "tetraspanin", "controls body size", "homeostatic processes", "tgf", "tsp"], "article_id"=>1417018, "categories"=>["Biological Sciences"], "users"=>["Zhiyu Liu", "Herong Shi", "Lindsey C. Szymczak", "Taner Aydin", "Sijung Yun", "Katharine Constas", "Arielle Schaeffer", "Sinthu Ranjan", "Saad Kubba", "Emad Alam", "Devin E. McMahon", "Jingpeng He", "Neta Shwartz", "Chenxi Tian", "Yevgeniy Plavskin", "Amanda Lindy", "Nimra Amir Dad", "Sunny Sheth", "Nirav M. Amin", "Stephanie Zimmerman", "Dennis Liu", "Erich M. Schwarz", "Harold Smith", "Michael W. Krause", "Jun Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005221.g005", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TSP_21_is_localized_to_the_plasma_membrane_of_multiple_cell_types_including_known_Sma_Mab_signal_receiving_cells_/1417018", "title"=>"TSP-21 is localized to the plasma membrane of multiple cell types, including known Sma/Mab signal-receiving cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-15 03:35:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/2070530"], "description"=>"<p>Diploid yeast cells expressing specific Cub- and Nub- fusion proteins were grown in SC-Ade,-His, Trp,-Leu,-Ura (SC-AHTLU) plates supplemented with 0.3mM of methionine. Cub and NubG were each used as negative controls. NubWT was used as a positive control to indicate expression of each Cub-PLV fusion protein. The potassium channel KAT1 was used as a control for specificity. KAT1 can interact with KAT1, but not with any of the proteins tested here.</p>", "links"=>[], "tags"=>["tumor progression", "spatiotemporal control", "Glycosphingolipids Bone", "prognostic markers", "cancer development", "Bone Morphogenetic Protein Signaling", "sma", "growth factor β", "postembryonic M lineage development", "BMP pathway", "tetraspanin", "controls body size", "homeostatic processes", "tgf", "tsp"], "article_id"=>1417021, "categories"=>["Biological Sciences"], "users"=>["Zhiyu Liu", "Herong Shi", "Lindsey C. Szymczak", "Taner Aydin", "Sijung Yun", "Katharine Constas", "Arielle Schaeffer", "Sinthu Ranjan", "Saad Kubba", "Emad Alam", "Devin E. McMahon", "Jingpeng He", "Neta Shwartz", "Chenxi Tian", "Yevgeniy Plavskin", "Amanda Lindy", "Nimra Amir Dad", "Sunny Sheth", "Nirav M. Amin", "Stephanie Zimmerman", "Dennis Liu", "Erich M. Schwarz", "Harold Smith", "Michael W. Krause", "Jun Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005221.g006", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Interactions_among_TSP_12_TSP_14_TSP_21_and_the_receptors_SMA_6_and_DAF_4_/1417021", "title"=>"Interactions among TSP-12, TSP-14, TSP-21 and the receptors SMA-6 and DAF-4.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-15 03:35:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/2070532"], "description"=>"<p>Tetraspanins TSP-21, TSP-12 and TSP-14 (collectively TSPs) interact with each other to organize membranes into microdomains that are enriched in glycosphingolipids (GSLs). Via interacting with the type I receptor SMA-6, the tetraspanins may recruit the receptors or the ligand-receptor complex (DBL-1/BMP, SMA-6/RI, DAF-4/RII) and their associated modulators (DRAG-1/RGM, UNC-40/neogenin and SMA-10/LRIG) to these microdomains, resulting in enhanced BMP signaling. Alternatively, but not mutually exclusively, these tetraspanins may function to regulate the trafficking of their associated receptor SMA-6 and possibly other components in the Sma/Mab pathway to promote BMP signaling.</p>", "links"=>[], "tags"=>["tumor progression", "spatiotemporal control", "Glycosphingolipids Bone", "prognostic markers", "cancer development", "Bone Morphogenetic Protein Signaling", "sma", "growth factor β", "postembryonic M lineage development", "BMP pathway", "tetraspanin", "controls body size", "homeostatic processes", "tgf", "tsp"], "article_id"=>1417023, "categories"=>["Biological Sciences"], "users"=>["Zhiyu Liu", "Herong Shi", "Lindsey C. Szymczak", "Taner Aydin", "Sijung Yun", "Katharine Constas", "Arielle Schaeffer", "Sinthu Ranjan", "Saad Kubba", "Emad Alam", "Devin E. McMahon", "Jingpeng He", "Neta Shwartz", "Chenxi Tian", "Yevgeniy Plavskin", "Amanda Lindy", "Nimra Amir Dad", "Sunny Sheth", "Nirav M. Amin", "Stephanie Zimmerman", "Dennis Liu", "Erich M. Schwarz", "Harold Smith", "Michael W. Krause", "Jun Liu"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1005221.g007", "stats"=>{"downloads"=>4, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Models_of_how_tetraspanin_proteins_function_to_promote_BMP_signaling_/1417023", "title"=>"Models of how tetraspanin proteins function to promote BMP signaling.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-15 03:35:18"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"14", "full-text"=>"15", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"3", "cited-by"=>"1", "year"=>"2018", "month"=>"10"}
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  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"15", "full-text"=>"14", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"1", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"74", "full-text"=>"77", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"18", "full-text"=>"18", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"14", "full-text"=>"10", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"14", "cited-by"=>"1", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"18", "full-text"=>"16", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"26", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}

Relative Metric

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