Fiche publication
Date publication
juillet 2025
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Pr THAUVIN-ROBINET Christel
Tous les auteurs :
Vazquez N, Lee C, Valenzuela I, Phan TP, Derderian C, Chávez M, Mooney NA, Demeter J, Aziz-Zanjani MO, Cusco I, Codina M, Martínez-Gil N, Valverde D, Solarat C, Buel AL, Thauvin-Robinet C, Steichen E, Filges I, Joset P, De Geyter J, Vaidyanathan K, Gardner TP, Toriyama M, Marcotte EM, Drew K, Roberson EC, Jackson PK, Reiter JF, Tizzano EF, Wallingford JB
Lien Pubmed
Résumé
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.
Mots clés
Humans, Ciliopathies, genetics, Cilia, metabolism, Male, Female, Orofaciodigital Syndromes, genetics, Basal Bodies, metabolism, Pedigree, Mutation, Phenotype
Référence
Nat Commun. 2025 07 1;16(1):5701
