The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture
Abstract Cilia are essential organelles, and variants in genes governing ciliary function result in ciliopathic diseases. The Ciliogenesis and PLANar polarity Effectors (CPLANE) protein complex is essential for ciliogenesis, and all but one subunit of the CPLANE complex have been implicated in human...
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61005-8 |
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| author | Neftalí Vazquez Chanjae Lee Irene Valenzuela Thao P. Phan Camille Derderian Marcelo Chávez Nancie A. Mooney Janos Demeter Mohammad Ovais Aziz-Zanjani Ivon Cusco Marta Codina Núria Martínez-Gil Diana Valverde Carlos Solarat Ange-Line Buel Cristel Thauvin-Robinet Elisabeth Steichen Isabel Filges Pascal Joset Julie De Geyter Krishna Vaidyanathan Tynan P. Gardner Michinori Toriyama Edward M. Marcotte Kevin Drew Elle C. Roberson Peter K. Jackson Jeremy F. Reiter Eduardo F. Tizzano John B. Wallingford |
| author_facet | Neftalí Vazquez Chanjae Lee Irene Valenzuela Thao P. Phan Camille Derderian Marcelo Chávez Nancie A. Mooney Janos Demeter Mohammad Ovais Aziz-Zanjani Ivon Cusco Marta Codina Núria Martínez-Gil Diana Valverde Carlos Solarat Ange-Line Buel Cristel Thauvin-Robinet Elisabeth Steichen Isabel Filges Pascal Joset Julie De Geyter Krishna Vaidyanathan Tynan P. Gardner Michinori Toriyama Edward M. Marcotte Kevin Drew Elle C. Roberson Peter K. Jackson Jeremy F. Reiter Eduardo F. Tizzano John B. Wallingford |
| author_sort | Neftalí Vazquez |
| collection | DOAJ |
| description | Abstract Cilia are essential organelles, and variants in genes governing ciliary function result in ciliopathic diseases. The Ciliogenesis and PLANar polarity Effectors (CPLANE) protein complex is essential for ciliogenesis, and all but one subunit of the CPLANE complex have been implicated in human ciliopathy. Here, we identify three families in which variants in the remaining CPLANE subunit CPLANE2/RSG1 also cause ciliopathy. These patients display cleft palate, tongue lobulations and polydactyly, phenotypes characteristic of Oral-Facial-Digital Syndrome. We further show that these alleles disrupt two vital steps of ciliogenesis, basal body docking and recruitment of intraflagellar transport proteins. Moreover, APMS reveals that Rsg1 binds CPLANE and the transition zone protein Fam92 in a GTP-dependent manner. Finally, we show that CPLANE is generally required for normal transition zone architecture. Our work demonstrates that CPLANE2/RSG1 is a causative gene for human ciliopathy and also sheds new light on the mechanisms of ciliary transition zone assembly. |
| format | Article |
| id | doaj-art-9a38d7d9b3174f34964d41218a0c5b5f |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-9a38d7d9b3174f34964d41218a0c5b5f2025-08-20T04:01:41ZengNature PortfolioNature Communications2041-17232025-07-0116111610.1038/s41467-025-61005-8The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architectureNeftalí Vazquez0Chanjae Lee1Irene Valenzuela2Thao P. Phan3Camille Derderian4Marcelo Chávez5Nancie A. Mooney6Janos Demeter7Mohammad Ovais Aziz-Zanjani8Ivon Cusco9Marta Codina10Núria Martínez-Gil11Diana Valverde12Carlos Solarat13Ange-Line Buel14Cristel Thauvin-Robinet15Elisabeth Steichen16Isabel Filges17Pascal Joset18Julie De Geyter19Krishna Vaidyanathan20Tynan P. Gardner21Michinori Toriyama22Edward M. Marcotte23Kevin Drew24Elle C. Roberson25Peter K. Jackson26Jeremy F. Reiter27Eduardo F. Tizzano28John B. Wallingford29Department of Molecular Biosciences, University of Texas at AustinDepartment of Molecular Biosciences, University of Texas at AustinDepartment of Clinical and Molecular Genetics, Vall d´Hebron University Hospital. European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability (ERN-ITHACA), Medicine Genetics Group, Vall d´Hebron Research InstituteDepartment of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San FranciscoDepartment of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San FranciscoBaxter Laboratory, Department of Microbiology & Immunology, Stanford University School of MedicineBaxter Laboratory, Department of Microbiology & Immunology, Stanford University School of MedicineBaxter Laboratory, Department of Microbiology & Immunology, Stanford University School of MedicineBaxter Laboratory, Department of Microbiology & Immunology, Stanford University School of MedicineDepartment of Clinical and Molecular Genetics, Vall d´Hebron University Hospital. European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability (ERN-ITHACA), Medicine Genetics Group, Vall d´Hebron Research InstituteDepartment of Clinical and Molecular Genetics, Vall d´Hebron University Hospital. European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability (ERN-ITHACA), Medicine Genetics Group, Vall d´Hebron Research InstituteDepartment of Clinical and Molecular Genetics, Vall d´Hebron University Hospital. European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability (ERN-ITHACA), Medicine Genetics Group, Vall d´Hebron Research InstituteCINBIO, University of Vigo and Research Group on Rare Diseases and Pediatric Medicine, Health Research Institute Galicia Sur (IIS Galicia Sur), SERGASUVIGOCINBIO, University of Vigo and Research Group on Rare Diseases and Pediatric Medicine, Health Research Institute Galicia Sur (IIS Galicia Sur), SERGASUVIGOFunctional Unity of Innovative Diagnosis for Rare Diseases and Inserm UMR1231 team GAD, University of BurgundyFunctional Unity of Innovative Diagnosis for Rare Diseases and Inserm UMR1231 team GAD, University of BurgundyDepartment of Pediatrics, Medical School, University of InnsbruckMedical Genetics, Institute of Medical Genetics and Pathology and Department of Clinical Research, University Hospital BaselMedical Genetics, Institute of Medical Genetics and Pathology and Department of Clinical Research, University Hospital BaselMedical Genetics, Institute of Medical Genetics and Pathology and Department of Clinical Research, University Hospital BaselDepartment of Molecular Biosciences, University of Texas at AustinDepartment of Molecular Biosciences, University of Texas at AustinDepartment of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, SandaDepartment of Molecular Biosciences, University of Texas at AustinDepartment of Biological Sciences, University of Illinois at ChicagoDevelopmental Biology and Pediatrics, CU Anschutz Medical CampusBaxter Laboratory, Department of Microbiology & Immunology, Stanford University School of MedicineDepartment of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California, San FranciscoDepartment of Clinical and Molecular Genetics, Vall d´Hebron University Hospital. European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability (ERN-ITHACA), Medicine Genetics Group, Vall d´Hebron Research InstituteDepartment of Molecular Biosciences, University of Texas at AustinAbstract Cilia are essential organelles, and variants in genes governing ciliary function result in ciliopathic diseases. The Ciliogenesis and PLANar polarity Effectors (CPLANE) protein complex is essential for ciliogenesis, and all but one subunit of the CPLANE complex have been implicated in human ciliopathy. Here, we identify three families in which variants in the remaining CPLANE subunit CPLANE2/RSG1 also cause ciliopathy. These patients display cleft palate, tongue lobulations and polydactyly, phenotypes characteristic of Oral-Facial-Digital Syndrome. We further show that these alleles disrupt two vital steps of ciliogenesis, basal body docking and recruitment of intraflagellar transport proteins. Moreover, APMS reveals that Rsg1 binds CPLANE and the transition zone protein Fam92 in a GTP-dependent manner. Finally, we show that CPLANE is generally required for normal transition zone architecture. Our work demonstrates that CPLANE2/RSG1 is a causative gene for human ciliopathy and also sheds new light on the mechanisms of ciliary transition zone assembly.https://doi.org/10.1038/s41467-025-61005-8 |
| spellingShingle | Neftalí Vazquez Chanjae Lee Irene Valenzuela Thao P. Phan Camille Derderian Marcelo Chávez Nancie A. Mooney Janos Demeter Mohammad Ovais Aziz-Zanjani Ivon Cusco Marta Codina Núria Martínez-Gil Diana Valverde Carlos Solarat Ange-Line Buel Cristel Thauvin-Robinet Elisabeth Steichen Isabel Filges Pascal Joset Julie De Geyter Krishna Vaidyanathan Tynan P. Gardner Michinori Toriyama Edward M. Marcotte Kevin Drew Elle C. Roberson Peter K. Jackson Jeremy F. Reiter Eduardo F. Tizzano John B. Wallingford The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture Nature Communications |
| title | The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture |
| title_full | The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture |
| title_fullStr | The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture |
| title_full_unstemmed | The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture |
| title_short | The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture |
| title_sort | human ciliopathy protein rsg1 links the cplane complex to transition zone architecture |
| url | https://doi.org/10.1038/s41467-025-61005-8 |
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