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<p>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 <i>CPLANE2/RSG1</i> 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 <i>CPLANE2/RSG1</i> is a causative gene for human ciliopathy and also sheds new light on the mechanisms of ciliary transition zone assembly.</p>

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The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月1日

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  • 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 Bruel,
  • 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

摘要

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.