Florian Rouaud, Marine Maupérin, Annick Mutero-Maeda, Sandra Citi
{"title":"肌球蛋白与非肌球蛋白的相互作用在上皮细胞形态发生和肌球蛋白纳米级组织中发挥作用。","authors":"Florian Rouaud, Marine Maupérin, Annick Mutero-Maeda, Sandra Citi","doi":"10.1242/jcs.262353","DOIUrl":null,"url":null,"abstract":"<p><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-nonmuscle myosin 2 (NM2) interaction in epithelial morphogenesis and nanoscale organization of CGN by expressing wild-type and mutant CGN constructs in CGN-knockout Madin-Darby 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.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"137 18","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449440/pdf/","citationCount":"0","resultStr":"{\"title\":\"Cingulin-nonmuscle myosin interaction plays a role in epithelial morphogenesis and cingulin nanoscale organization.\",\"authors\":\"Florian Rouaud, Marine Maupérin, Annick Mutero-Maeda, Sandra Citi\",\"doi\":\"10.1242/jcs.262353\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><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-nonmuscle myosin 2 (NM2) interaction in epithelial morphogenesis and nanoscale organization of CGN by expressing wild-type and mutant CGN constructs in CGN-knockout Madin-Darby 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.</p>\",\"PeriodicalId\":15227,\"journal\":{\"name\":\"Journal of cell science\",\"volume\":\"137 18\",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-09-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449440/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of cell science\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1242/jcs.262353\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/25 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of cell science","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1242/jcs.262353","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/25 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Cingulin-nonmuscle myosin interaction plays a role in epithelial morphogenesis and cingulin nanoscale organization.
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-nonmuscle myosin 2 (NM2) interaction in epithelial morphogenesis and nanoscale organization of CGN by expressing wild-type and mutant CGN constructs in CGN-knockout Madin-Darby 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.