{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T07:08:36Z","timestamp":1772176116109,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pgen.1009936","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:00:00Z","timestamp":1644364800000}}],"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T00:00:00Z","timestamp":1643328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01 GM103869"],"award-info":[{"award-number":["R01 GM103869"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35 GM130351"],"award-info":[{"award-number":["R35 GM130351"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P40 OD010440"],"award-info":[{"award-number":["P40 OD010440"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012636","name":"New York State Stem Cell Science","doi-asserted-by":"publisher","award":["CO29155"],"award-info":[{"award-number":["CO29155"]}],"id":[{"id":"10.13039\/100012636","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10OD018516"],"award-info":[{"award-number":["S10OD018516"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Tetraspanin proteins are a unique family of highly conserved four-pass transmembrane proteins in metazoans. While much is known about their biochemical properties, the in vivo functions and distribution patterns of different tetraspanin proteins are less understood. Previous studies have shown that two paralogous tetraspanins that belong to the TspanC8 subfamily, TSP-12 and TSP-14, function redundantly to promote both Notch signaling and\n                    <jats:underline>b<\/jats:underline>\n                    one\n                    <jats:underline>m<\/jats:underline>\n                    orphogenetic\n                    <jats:underline>p<\/jats:underline>\n                    rotein (BMP) signaling in\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>elegans<\/jats:italic>\n                    . TSP-14 has two isoforms, TSP-14A and TSP-14B, where TSP-14B has an additional 24 amino acids at its N-terminus compared to TSP-14A. By generating isoform specific knock-ins and knock-outs using CRISPR, we found that TSP-14A and TSP-14B share distinct as well as overlapping expression patterns and functions. While TSP-14A functions redundantly with TSP-12 to regulate body size and embryonic and vulva development, TSP-14B primarily functions redundantly with TSP-12 to regulate postembryonic mesoderm development. Importantly, TSP-14A and TSP-14B exhibit distinct subcellular localization patterns. TSP-14A is localized apically and on early and late endosomes. TSP-14B is localized to the basolateral cell membrane. We further identified a di-leucine motif within the N-terminal 24 amino acids of TSP-14B that serves as a basolateral membrane targeting sequence, and showed that the basolateral membrane localization of TSP-14B is important for its function. Our work highlights the diverse and intricate functions of TspanC8 tetraspanins in\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>elegans<\/jats:italic>\n                    , and demonstrates the importance of dissecting the functions of these important proteins in an intact living organism.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1009936","type":"journal-article","created":{"date-parts":[[2022,1,28]],"date-time":"2022-01-28T13:37:46Z","timestamp":1643377066000},"page":"e1009936","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["The C. elegans TspanC8 tetraspanin TSP-14 exhibits isoform-specific localization and function"],"prefix":"10.1371","volume":"18","author":[{"given":"Zhiyu","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7815-4075","authenticated-orcid":true,"given":"Jun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"issue":"10","key":"pgen.1009936.ref001","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/nrm1736","article-title":"Tetraspanin functions and associated microdomains","volume":"6","author":"ME Hemler","year":"2005","journal-title":"Nature reviewsMolecular cell biology"},{"key":"pgen.1009936.ref002","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3389\/fcell.2017.00034","article-title":"Tetraspanins Function as Regulators of Cellular Signaling","volume":"5","author":"CM Termini","year":"2017","journal-title":"Front Cell Dev Biol"},{"issue":"3","key":"pgen.1009936.ref003","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1042\/BST20160290","article-title":"Scissor sisters: regulation of ADAM10 by the TspanC8 tetraspanins","volume":"45","author":"AL Matthews","year":"2017","journal-title":"Biochem Soc Trans"},{"issue":"4","key":"pgen.1009936.ref004","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1042\/BST20160296","article-title":"Regulation of the trafficking and the function of the metalloprotease ADAM10 by tetraspanins","volume":"45","author":"J Saint-Pol","year":"2017","journal-title":"Biochem Soc Trans"},{"issue":"3","key":"pgen.1009936.ref005","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1083\/jcb.201201133","article-title":"TspanC8 tetraspanins regulate ADAM10\/Kuzbanian trafficking and promote Notch activation in flies and mammals","volume":"199","author":"E Dornier","year":"2012","journal-title":"The Journal of cell biology"},{"issue":"47","key":"pgen.1009936.ref006","doi-asserted-by":"crossref","first-page":"39753","DOI":"10.1074\/jbc.M112.416503","article-title":"The TspanC8 subgroup of tetraspanins interacts with A disintegrin and metalloprotease 10 (ADAM10) and regulates its maturation and cell surface expression","volume":"287","author":"EJ Haining","year":"2012","journal-title":"The Journal of biological chemistry"},{"issue":"17","key":"pgen.1009936.ref007","doi-asserted-by":"crossref","first-page":"2919","DOI":"10.1007\/s00018-012-0960-2","article-title":"Tetraspanin15 regulates cellular trafficking and activity of the ectodomain sheddase ADAM10. Cellular and molecular life sciences","volume":"69","author":"J Prox","year":"2012","journal-title":"CMLS"},{"issue":"36","key":"pgen.1009936.ref008","doi-asserted-by":"crossref","first-page":"12822","DOI":"10.1074\/jbc.RA120.012601","article-title":"The tetraspanin Tspan15 is an essential subunit of an ADAM10 scissor complex","volume":"295","author":"CZ Koo","year":"2020","journal-title":"J Biol Chem"},{"issue":"8","key":"pgen.1009936.ref009","doi-asserted-by":"crossref","first-page":"2132","DOI":"10.1016\/j.celrep.2018.10.088","article-title":"A Dock-and-Lock Mechanism Clusters ADAM10 at Cell-Cell Junctions to Promote alpha-Toxin Cytotoxicity","volume":"25","author":"J Shah","year":"2018","journal-title":"Cell Rep"},{"issue":"1","key":"pgen.1009936.ref010","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/sji.12559","article-title":"Tspan33 is Expressed in Transitional and Memory B Cells, but is not Responsible for High ADAM10 Expression","volume":"86","author":"CA Perez-Martinez","year":"2017","journal-title":"Scand J Immunol"},{"issue":"17","key":"pgen.1009936.ref011","doi-asserted-by":"crossref","first-page":"3251","DOI":"10.1007\/s00018-018-2791-2","article-title":"In vivo regulation of the A disintegrin and metalloproteinase 10 (ADAM10) by the tetraspanin 15","volume":"75","author":"L Seipold","year":"2018","journal-title":"Cell Mol Life Sci"},{"issue":"1","key":"pgen.1009936.ref012","doi-asserted-by":"crossref","DOI":"10.26508\/lsa.201900444","article-title":"TspanC8 tetraspanins differentially regulate ADAM10 endocytosis and half-life","volume":"3","author":"E Eschenbrenner","year":"2020","journal-title":"Life Sci Alliance"},{"issue":"13","key":"pgen.1009936.ref013","doi-asserted-by":"crossref","first-page":"5907","DOI":"10.1073\/pnas.1001647107","article-title":"A conserved tetraspanin subfamily promotes Notch signaling in Caenorhabditis elegans and in human cells","volume":"107","author":"CD Dunn","year":"2010","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"5","key":"pgen.1009936.ref014","doi-asserted-by":"crossref","first-page":"e1005221","DOI":"10.1371\/journal.pgen.1005221","article-title":"Promotion of bone morphogenetic protein signaling by tetraspanins and glycosphingolipids","volume":"11","author":"Z Liu","year":"2015","journal-title":"PLoS Genet"},{"issue":"1","key":"pgen.1009936.ref015","doi-asserted-by":"crossref","first-page":"e1006568","DOI":"10.1371\/journal.pgen.1006568","article-title":"Two Paralogous Tetraspanins TSP-12 and TSP-14 Function with the ADAM10 Metalloprotease SUP-17 to Promote BMP Signaling in Caenorhabditis elegans","volume":"13","author":"L Wang","year":"2017","journal-title":"PLoS Genet"},{"issue":"6","key":"pgen.1009936.ref016","doi-asserted-by":"crossref","first-page":"2968","DOI":"10.1073\/pnas.1918807117","article-title":"Tetraspanins TSP-12 and TSP-14 function redundantly to regulate the trafficking of the type II BMP receptor in Caenorhabditis elegans","volume":"117","author":"Z Liu","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"pgen.1009936.ref017","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a022178","article-title":"The TGF-beta Family in Caenorhabditis elegans","volume":"9","author":"C Savage-Dunn","year":"2017","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"11","key":"pgen.1009936.ref018","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1038\/ng.248","article-title":"Single-copy insertion of transgenes in Caenorhabditis elegans","volume":"40","author":"C Frokjaer-Jensen","year":"2008","journal-title":"Nat Genet"},{"issue":"19","key":"pgen.1009936.ref019","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1016\/j.cub.2008.08.013","article-title":"3\u2019 UTRs are the primary regulators of gene expression in the C. elegans germline","volume":"18","author":"C Merritt","year":"2008","journal-title":"Curr Biol"},{"issue":"11","key":"pgen.1009936.ref020","doi-asserted-by":"crossref","first-page":"a016790","DOI":"10.1101\/cshperspect.a016790","article-title":"Cargo recognition in clathrin-mediated endocytosis","volume":"5","author":"LM Traub","year":"2013","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"pgen.1009936.ref021","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1146\/annurev.biochem.72.121801.161800","article-title":"Signals for sorting of transmembrane proteins to endosomes and lysosomes","volume":"72","author":"JS Bonifacino","year":"2003","journal-title":"Annu Rev Biochem"},{"issue":"3","key":"pgen.1009936.ref022","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/0092-8674(92)90508-A","article-title":"Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development","volume":"71","author":"MA Rudnicki","year":"1992","journal-title":"Cell"},{"issue":"6568","key":"pgen.1009936.ref023","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/379823a0","article-title":"Functional redundancy of the muscle-specific transcription factors Myf5 and myogenin","volume":"379","author":"Y Wang","year":"1996","journal-title":"Nature"},{"issue":"8","key":"pgen.1009936.ref024","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1091\/mbc.11.8.2743","article-title":"Distinct and redundant functions of mu1 medium chains of the AP-1 clathrin-associated protein complex in the nematode Caenorhabditis elegans","volume":"11","author":"J Shim","year":"2000","journal-title":"Mol Biol Cell"},{"issue":"11","key":"pgen.1009936.ref025","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1242\/dev.076711","article-title":"AP-1 is required for the maintenance of apico-basal polarity in the C. elegans intestine","volume":"139","author":"M Shafaq-Zadah","year":"2012","journal-title":"Development"},{"issue":"11","key":"pgen.1009936.ref026","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1242\/dev.077347","article-title":"Clathrin and AP-1 regulate apical polarity and lumen formation during C. elegans tubulogenesis","volume":"139","author":"H Zhang","year":"2012","journal-title":"Development"},{"issue":"1","key":"pgen.1009936.ref027","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.devcel.2007.12.001","article-title":"C. elegans AP-2 and retromer control Wnt signaling by regulating mig-14\/Wntless","volume":"14","author":"CL Pan","year":"2008","journal-title":"Dev Cell"},{"issue":"23","key":"pgen.1009936.ref028","doi-asserted-by":"crossref","first-page":"9551","DOI":"10.1074\/jbc.M116.765669","article-title":"New insights into the tetraspanin Tspan5 using novel monoclonal antibodies","volume":"292","author":"J Saint-Pol","year":"2017","journal-title":"J Biol Chem"},{"key":"pgen.1009936.ref029","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/978-1-4939-8904-1_6","article-title":"Mutagenesis and Imaging Studies of BMP Signaling Mechanisms in C. elegans","volume":"1891","author":"C Savage-Dunn","year":"2019","journal-title":"Methods Mol Biol"},{"issue":"2","key":"pgen.1009936.ref030","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.1600-0854.2006.00515.x","article-title":"Tetraspanins as regulators of protein trafficking","volume":"8","author":"F Berditchevski","year":"2007","journal-title":"Traffic"},{"issue":"4","key":"pgen.1009936.ref031","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s00430-020-00673-3","article-title":"Tetraspanins: integrating cell surface receptors to functional microdomains in homeostasis and disease","volume":"209","author":"D Kummer","year":"2020","journal-title":"Med Microbiol Immunol"},{"issue":"2","key":"pgen.1009936.ref032","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.tcb.2020.11.004","article-title":"Dynamic Plasma Membrane Organization: A Complex Symphony","volume":"31","author":"S van Deventer","year":"2021","journal-title":"Trends Cell Biol"},{"issue":"1","key":"pgen.1009936.ref033","first-page":"40","article-title":"Tetraspanins: push and pull in suppressing and promoting metastasis","volume":"9","author":"M. Zoller","year":"2009","journal-title":"Nature reviewsCancer"},{"issue":"1","key":"pgen.1009936.ref034","first-page":"49","article-title":"Tetraspanin proteins promote multiple cancer stages","volume":"14","author":"ME Hemler","year":"2014","journal-title":"Nature reviewsCancer"},{"issue":"13","key":"pgen.1009936.ref035","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22136707","article-title":"Regulation of ADAM10 by the TspanC8 Family of Tetraspanins and Their Therapeutic Potential.","volume":"22","author":"N Harrison","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"19","key":"pgen.1009936.ref036","doi-asserted-by":"crossref","first-page":"4070","DOI":"10.1242\/dev.099838","article-title":"The neogenin\/DCC homolog UNC-40 promotes BMP signaling via the RGM protein DRAG-1 in C. elegans","volume":"140","author":"C Tian","year":"2013","journal-title":"Development (Cambridge, England)."},{"issue":"3","key":"pgen.1009936.ref037","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1534\/genetics.114.169730","article-title":"Efficient marker-free recovery of custom genetic modifications with CRISPR\/Cas9 in Caenorhabditis elegans","volume":"198","author":"JA Arribere","year":"2014","journal-title":"Genetics"},{"issue":"4","key":"pgen.1009936.ref038","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1534\/genetics.115.178335","article-title":"Streamlined Genome Engineering with a Self-Excising Drug Selection Cassette","volume":"200","author":"DJ Dickinson","year":"2015","journal-title":"Genetics"},{"key":"pgen.1009936.ref039","article-title":"Direct visualization of a native Wnt in vivo reveals that a long-range Wnt gradient forms by extracellular dispersal","volume":"7","author":"AM Pani","year":"2018","journal-title":"Elife"},{"issue":"7","key":"pgen.1009936.ref040","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"J Schindelin","year":"2012","journal-title":"Nat Methods"},{"issue":"3","key":"pgen.1009936.ref041","doi-asserted-by":"crossref","DOI":"10.1242\/jcs.211847","article-title":"Image co-localization\u2014co-occurrence versus correlation","volume":"131","author":"JS Aaron","year":"2018","journal-title":"J Cell Sci"}],"updated-by":[{"DOI":"10.1371\/journal.pgen.1009936","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:00:00Z","timestamp":1644364800000}}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1009936","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T13:43:02Z","timestamp":1644414182000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1009936"}},"subtitle":[],"editor":[{"given":"Iva","family":"Greenwald","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,1,28]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1009936","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.11.10.468015","asserted-by":"object"}]},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,28]]}}}