{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T06:55:01Z","timestamp":1785826501977,"version":"3.56.0"},"reference-count":46,"publisher":"The Company of Biologists","issue":"18","license":[{"start":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T00:00:00Z","timestamp":1727222400000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"crossref","award":["31003A_135730"],"award-info":[{"award-number":["31003A_135730"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"crossref","award":["310030_200681"],"award-info":[{"award-number":["310030_200681"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"crossref","award":["31003A_172809"],"award-info":[{"award-number":["31003A_172809"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"crossref","award":["31003A_152899"],"award-info":[{"award-number":["31003A_152899"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011723","name":"Canton de Gen\u00e8ve","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100011723","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100006389","name":"Universit\u00e9 de Gen\u00e8ve","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006389","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Cingulin (CGN) tethers nonmuscle myosin 2B (NM2B; heavy chain encoded by MYH10) to tight junctions (TJs) to modulate junctional and apical cortex mechanics. Here, we studied the role of the CGN\u2013nonmuscle myosin 2 (NM2) interaction in epithelial morphogenesis and nanoscale organization of CGN by expressing wild-type and mutant CGN constructs in CGN-knockout Madin\u2013Darby canine kidney (MDCK) epithelial cells. We show that the NM2-binding region of CGN is required to promote normal cyst morphogenesis of MDCK cells grown in three dimensions and to maintain the C-terminus of CGN in a distal position with respect to the ZO-2 (or TJP2)-containing TJ submembrane region, whereas the N-terminus of CGN is localized more proximal to the TJ membrane. We also show that the CGN mutant protein that causes deafness in human and mouse models is localized at TJs but does not bind to NM2B, resulting in decreased TJ membrane tortuosity. These results indicate that the interaction between CGN and NM2B regulates epithelial tissue morphogenesis and nanoscale organization of CGN and suggest that CGN regulates the auditory function of hair cells by organizing the actomyosin cytoskeleton to modulate the mechanics of the apical and junctional cortex.<\/jats:p>","DOI":"10.1242\/jcs.262353","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T15:47:35Z","timestamp":1727279255000},"source":"Crossref","is-referenced-by-count":3,"title":["Cingulin\u2013nonmuscle myosin interaction plays a role in epithelial morphogenesis and cingulin nanoscale organization"],"prefix":"10.1242","volume":"137","author":[{"given":"Florian","family":"Rouaud","sequence":"first","affiliation":[{"name":"University of Geneva Department of Molecular and Cellular Biology , , 30, Quai E. Ansermet, 1205 Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Maup\u00e9rin","sequence":"additional","affiliation":[{"name":"University of Geneva Department of Molecular and Cellular Biology , , 30, Quai E. Ansermet, 1205 Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annick","family":"Mutero-Maeda","sequence":"additional","affiliation":[{"name":"University of Geneva Department of Molecular and Cellular Biology , , 30, Quai E. Ansermet, 1205 Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6537-4818","authenticated-orcid":false,"given":"Sandra","family":"Citi","sequence":"additional","affiliation":[{"name":"University of Geneva Department of Molecular and Cellular Biology , , 30, Quai E. Ansermet, 1205 Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,9,25]]},"reference":[{"key":"2024092509532417300_JCS262353C1","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1016\/j.devcel.2005.03.003","article-title":"Binding of GEF-H1 to the tight junction-associated adaptor cingulin results in inhibition of Rho signaling and G1\/S phase transition","volume":"8","author":"Aijaz","year":"2005","journal-title":"Dev. Cell"},{"key":"2024092509532417300_JCS262353C2","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1016\/j.devcel.2020.07.022","article-title":"A weak link with actin organizes tight junctions to control epithelial permeability","volume":"54","author":"Belardi","year":"2020","journal-title":"Dev. Cell"},{"key":"2024092509532417300_JCS262353C3","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1016\/j.cell.2019.10.011","article-title":"Phase separation of zonula occludens proteins drives formation of tight junctions","volume":"179","author":"Beutel","year":"2019","journal-title":"Cell"},{"key":"2024092509532417300_JCS262353C4","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1146\/annurev-cellbio-100814-125323","article-title":"Polarized protein transport and lumen formation during epithelial tissue morphogenesis","volume":"31","author":"Blasky","year":"2015","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"2024092509532417300_JCS262353C5","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1038\/ncb2106","article-title":"A molecular network for de novo generation of the apical surface and lumen","volume":"12","author":"Bryant","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"2024092509532417300_JCS262353C6","doi-asserted-by":"publisher","first-page":"a029314","DOI":"10.1101\/cshperspect.a029314","article-title":"Cell biology of tight junction barrier regulation and mucosal disease","volume":"10","author":"Buckley","year":"2018","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"2024092509532417300_JCS262353C7","doi-asserted-by":"publisher","first-page":"R445","DOI":"10.1016\/j.cub.2018.02.003","article-title":"Tensile forces and mechanotransduction at cell-cell junctions","volume":"28","author":"Charras","year":"2018","journal-title":"Curr. Biol."},{"key":"2024092509532417300_JCS262353C8","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1007\/s12551-019-00582-7","article-title":"The mechanobiology of tight junctions","volume":"11","author":"Citi","year":"2019","journal-title":"Biophys. Rev."},{"key":"2024092509532417300_JCS262353C9","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/333272a0","article-title":"Cingulin, a new peripheral component of tight junctions","volume":"333","author":"Citi","year":"1988","journal-title":"Nature"},{"key":"2024092509532417300_JCS262353C10","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1111\/j.1749-6632.2012.06506.x","article-title":"Cingulin, paracingulin, and PLEKHA7: signaling and cytoskeletal adaptors at the apical junctional complex","volume":"1257","author":"Citi","year":"2012","journal-title":"Ann. NY Acad. Sci."},{"key":"2024092509532417300_JCS262353C11","doi-asserted-by":"publisher","first-page":"jcs261776","DOI":"10.1242\/jcs.261776","article-title":"A short guide to the tight junction","volume":"137","author":"Citi","year":"2024","journal-title":"J. Cell Sci."},{"key":"2024092509532417300_JCS262353C12","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1083\/jcb.147.7.1569","article-title":"Cingulin contains globular and coiled-coil domains and interacts with ZO-1, ZO-2, ZO-3, and myosin","volume":"147","author":"Cordenonsi","year":"1999","journal-title":"J. Cell Biol."},{"key":"2024092509532417300_JCS262353C13","doi-asserted-by":"publisher","first-page":"27757","DOI":"10.1074\/jbc.M203717200","article-title":"Evidence for a functional interaction between cingulin and ZO-1 in cultured cells","volume":"277","author":"D'Atri","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2024092509532417300_JCS262353C14","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/S1046-2023(03)00032-X","article-title":"Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures","volume":"30","author":"Debnath","year":"2003","journal-title":"Methods"},{"key":"2024092509532417300_JCS262353C15","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1038\/s41467-019-09074-4","article-title":"LMO7 deficiency reveals the significance of the cuticular plate for hearing function","volume":"10","author":"Du","year":"2019","journal-title":"Nat. Commun."},{"key":"2024092509532417300_JCS262353C16","doi-asserted-by":"publisher","first-page":"895703","DOI":"10.3389\/fphar.2022.895703","article-title":"Cytoplasmic beta and gamma actin isoforms reorganization and regulation in tumor cells in culture and tissue","volume":"13","author":"Dugina","year":"2022","journal-title":"Front. Pharmacol."},{"key":"2024092509532417300_JCS262353C17","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/j.cub.2013.03.039","article-title":"NMII forms a contractile transcellular sarcomeric network to regulate apical cell junctions and tissue geometry","volume":"23","author":"Ebrahim","year":"2013","journal-title":"Curr. Biol."},{"key":"2024092509532417300_JCS262353C18","doi-asserted-by":"publisher","first-page":"29745","DOI":"10.1074\/jbc.273.45.29745","article-title":"The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton","volume":"273","author":"Fanning","year":"1998","journal-title":"J. Biol. Chem."},{"key":"2024092509532417300_JCS262353C19","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1083\/jcb.17.2.375","article-title":"Junctional complexes in various epithelia","volume":"17","author":"Farquhar","year":"1963","journal-title":"J. Cell Biol."},{"key":"2024092509532417300_JCS262353C20","doi-asserted-by":"publisher","first-page":"jcs260745","DOI":"10.1242\/jcs.260745","article-title":"Paracingulin recruits CAMSAP3 to tight junctions and regulates microtubule and polarized epithelial cell organization","volume":"137","author":"Flinois","year":"2024","journal-title":"J. Cell Sci."},{"key":"2024092509532417300_JCS262353C21","doi-asserted-by":"publisher","first-page":"3569","DOI":"10.1091\/mbc.e06-02-0122","article-title":"Cingulin regulates claudin-2 expression and cell proliferation through the small GTPase RhoA","volume":"17","author":"Guillemot","year":"2006","journal-title":"Mol. Biol. Cell"},{"key":"2024092509532417300_JCS262353C22","doi-asserted-by":"publisher","first-page":"5245","DOI":"10.1242\/jcs.01399","article-title":"Disruption of the cingulin gene does not prevent tight junction formation but alters gene expression","volume":"117","author":"Guillemot","year":"2004","journal-title":"J. Cell Sci."},{"key":"2024092509532417300_JCS262353C23","doi-asserted-by":"publisher","first-page":"5005","DOI":"10.1242\/jcs.101261","article-title":"Cingulin is dispensable for epithelial barrier function and tight junction structure, and plays a role in the control of claudin-2 expression and response to duodenal mucosa injury","volume":"125","author":"Guillemot","year":"2012","journal-title":"J. Cell Sci."},{"key":"2024092509532417300_JCS262353C24","doi-asserted-by":"publisher","first-page":"e46599","DOI":"10.7554\/eLife.46599","article-title":"Myosin II isoforms play distinct roles in adherens junction biogenesis","volume":"8","author":"Heuze","year":"2019","journal-title":"Elife"},{"key":"2024092509532417300_JCS262353C25","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/s41575-023-00766-3","article-title":"Paracellular permeability and tight junction regulation in gut health and disease","volume":"20","author":"Horowitz","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"2024092509532417300_JCS262353C26","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1002\/embr.201338128","article-title":"FIP5 phosphorylation during mitosis regulates apical trafficking and lumenogenesis","volume":"15","author":"Li","year":"2014","journal-title":"EMBO Rep."},{"key":"2024092509532417300_JCS262353C27","doi-asserted-by":"publisher","first-page":"R815","DOI":"10.1016\/j.cub.2014.06.068","article-title":"Epithelial homeostasis","volume":"24","author":"Macara","year":"2014","journal-title":"Curr. Biol."},{"key":"2024092509532417300_JCS262353C28","doi-asserted-by":"publisher","first-page":"12426","DOI":"10.1038\/ncomms12426","article-title":"Cingulin and actin mediate midbody-dependent apical lumen formation during polarization of epithelial cells","volume":"7","author":"Mangan","year":"2016","journal-title":"Nat. Commun."},{"key":"2024092509532417300_JCS262353C29","doi-asserted-by":"publisher","first-page":"e202307104","DOI":"10.1083\/jcb.202307104","article-title":"Tight junction membrane proteins regulate the mechanical resistance of the apical junctional complex","volume":"223","author":"Nguyen","year":"2024","journal-title":"J. Cell Biol."},{"key":"2024092509532417300_JCS262353C30","doi-asserted-by":"publisher","first-page":"7989","DOI":"10.1038\/s41467-023-43653-w","article-title":"Cytosolic actin isoforms form networks with different rheological properties that indicate specific biological function","volume":"14","author":"Nietmann","year":"2023","journal-title":"Nat. Commun."},{"key":"2024092509532417300_JCS262353C31","doi-asserted-by":"publisher","first-page":"183399","DOI":"10.1016\/j.bbamem.2020.183399","article-title":"Scaffolding proteins of vertebrate apical junctions: structure, functions and biophysics","volume":"1862","author":"Rouaud","year":"2020","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"2024092509532417300_JCS262353C32","doi-asserted-by":"publisher","first-page":"e202208065","DOI":"10.1083\/jcb.202208065","article-title":"Cingulin and paracingulin tether myosins-2 to junctions to mechanoregulate the plasma membrane","volume":"322","author":"Rouaud","year":"2023","journal-title":"J. Cell Biol."},{"key":"2024092509532417300_JCS262353C33","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1016\/j.cell.2019.10.006","article-title":"Mechanosensation of tight junctions depends on ZO-1 phase separation and flow","volume":"179","author":"Schwayer","year":"2019","journal-title":"Cell"},{"key":"2024092509532417300_JCS262353C34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1091\/mbc.E21-07-0355","article-title":"PLEKHA5, PLEKHA6 and PLEKHA7 bind to PDZD11 to target the Menkes ATPase ATP7A to the cell periphery and regulate copper homeostasis","volume":"32","author":"Sluysmans","year":"2021","journal-title":"Mol. Biol. Cell"},{"key":"2024092509532417300_JCS262353C35","doi-asserted-by":"publisher","first-page":"3783","DOI":"10.1016\/j.cub.2017.11.014","article-title":"Tension-dependent stretching activates ZO-1 to control the junctional localization of its interactors","volume":"27","author":"Spadaro","year":"2017","journal-title":"Curr. Biol."},{"key":"2024092509532417300_JCS262353C36","doi-asserted-by":"publisher","first-page":"e104994","DOI":"10.1371\/journal.pone.0104994","article-title":"ZO-1 knockout by TALEN-mediated gene targeting in MDCK cells: involvement of ZO-1 in the regulation of cytoskeleton and cell shape","volume":"9","author":"Tokuda","year":"2014","journal-title":"PLoS One"},{"key":"2024092509532417300_JCS262353C37","doi-asserted-by":"publisher","first-page":"44785","DOI":"10.1074\/jbc.M406563200","article-title":"Establishment and characterization of cultured epithelial cells lacking expression of ZO-1","volume":"279","author":"Umeda","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2024092509532417300_JCS262353C38","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.semcdb.2014.08.011","article-title":"Architecture of tight junctions and principles of molecular composition","volume":"36","author":"Van Itallie","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"2024092509532417300_JCS262353C39","doi-asserted-by":"publisher","first-page":"jcs229286","DOI":"10.1242\/jcs.229286","article-title":"Multiscale dynamics of tight junction remodeling","volume":"132","author":"Varadarajan","year":"2019","journal-title":"J. Cell Sci."},{"key":"2024092509532417300_JCS262353C40","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1111\/nyas.13391","article-title":"Cell-specific diversity in the expression and organization of cytoplasmic plaque proteins of apical junctions","volume":"1405","author":"Vasileva","year":"2017","journal-title":"Ann. NY. Acad. Sci."},{"key":"2024092509532417300_JCS262353C41","doi-asserted-by":"publisher","first-page":"101797","DOI":"10.1016\/j.jbc.2022.101797","article-title":"Cingulin binds to the ZU5 domain of scaffolding protein ZO-1 to promote its extended conformation, stabilization, and tight junction accumulation","volume":"298","author":"Vasileva","year":"2022","journal-title":"J. Biol. Chem."},{"key":"2024092509532417300_JCS262353C42","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1083\/jcb.201304194","article-title":"The association of microtubules with tight junctions is promoted by cingulin phosphorylation by AMPK","volume":"203","author":"Yano","year":"2013","journal-title":"J. Cell Biol."},{"key":"2024092509532417300_JCS262353C43","doi-asserted-by":"publisher","first-page":"15550","DOI":"10.1038\/s41598-018-33418-7","article-title":"AMPK-dependent phosphorylation of cingulin reversibly regulates its binding to actin filaments and microtubules","volume":"8","author":"Yano","year":"2018","journal-title":"Sci. Rep."},{"key":"2024092509532417300_JCS262353C44","doi-asserted-by":"publisher","first-page":"a028761","DOI":"10.1101\/cshperspect.a028761","article-title":"Mechanosensing and mechanotransduction at cell-cell junctions","volume":"10","author":"Yap","year":"2017","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"2024092509532417300_JCS262353C45","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1086\/379286","article-title":"Mutations in the gamma-actin gene (ACTG1) are associated with dominant progressive deafness (DFNA20\/26)","volume":"73","author":"Zhu","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"2024092509532417300_JCS262353C46","doi-asserted-by":"publisher","first-page":"e17611","DOI":"10.15252\/emmm.202317611","article-title":"Cingulin regulates hair cell cuticular plate morphology and is required for hearing in human and mouse","volume":"15","author":"Zhu","year":"2023","journal-title":"EMBO Mol. Med."}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.262353\/3567708\/jcs262353.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/jcs\/article-pdf\/doi\/10.1242\/jcs.262353\/3567708\/jcs262353.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T15:47:37Z","timestamp":1727279257000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/137\/18\/jcs262353\/362134\/Cingulin-nonmuscle-myosin-interaction-plays-a-role"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,15]]},"references-count":46,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2024,9,15]]}},"URL":"https:\/\/doi.org\/10.1242\/jcs.262353","relation":{},"ISSN":["0021-9533","1477-9137"],"issn-type":[{"value":"0021-9533","type":"print"},{"value":"1477-9137","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,15]]},"article-number":"jcs262353"}}