The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture
Vazquez, Neftalí (University of Texas at Austin)
Lee, Chanjae (University of Texas at Austin)
Valenzuela, Irene (Universitat Autònoma de Barcelona)
Phan, Thao P (University of California)
Derderian, Camille (University of California)
Chávez, Marcelo (Stanford University School of Medicine, Stanford)
Mooney, Nancie A (Stanford University School of Medicine, Stanford)
Demeter, Janos (Stanford University School of Medicine, Stanford)
Aziz-Zanjani, Mohammad Ovais (Stanford University School of Medicine, Stanford)
Cusco, Ivon (Hospital Universitari Vall d'Hebron)
Martinez-Gil, Nuria (Hospital Universitari Vall d'Hebron)
Valverde, Diana (Instituto de Investigación Sanitaria Galicia Sur (IIS Galicia Sur))
Solarat, Carlos (Instituto de Investigación Sanitaria Galicia Sur (IIS Galicia Sur))
Buel, Ange Line (University of Burgundy)
Thauvin-Robinet, Cristel (University of Burgundy)
Steichen, Elisabeth (University of Innsbruck)
Filges, Isabel (University Hospital Basel (Basilea, Suïssa))
Joset, Pascal (University Hospital Basel (Basilea, Suïssa))
De Geyter, Julie (University Hospital Basel (Basilea, Suïssa))
Vaidyanathan, Krishna (University of Texas at Austin)
Gardner, Tynan P (University of Texas at Austin)
Toriyama, Michinori (Kwansei Gakuin University)
Marcotte, Edward M. (University of Texas at Austin)
Drew, Kevin (University of Illinois at Chicago)
Roberson, Elle C (CU Anschutz Medical Campus)
Jackson, Peter K. (Stanford University School of Medicine, Stanford)
Reiter, Jeremy F. (University of California)
Tizzano, Eduardo F. (Hospital Universitari Vall d'Hebron)
Wallingford, John B. (University of Texas at Austin)

Data:	2025
Resum:	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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Nature communications, Vol. 16, Num. 1 (July 2025) , art. 5701, ISSN 2041-1723

DOI: 10.1038/s41467-025-61005-8

16 p, 12.1 MB

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