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

Author

Listed:
  • Neftalí Vazquez

    (University of Texas at Austin)

  • Chanjae Lee

    (University of Texas at Austin)

  • Irene Valenzuela

    (Vall d´Hebron Research Institute)

  • Thao P. Phan

    (San Francisco)

  • Camille Derderian

    (San Francisco)

  • Marcelo Chávez

    (Stanford University School of Medicine)

  • Nancie A. Mooney

    (Stanford University School of Medicine)

  • Janos Demeter

    (Stanford University School of Medicine)

  • Mohammad Ovais Aziz-Zanjani

    (Stanford University School of Medicine)

  • Ivon Cusco

    (Vall d´Hebron Research Institute)

  • Marta Codina

    (Vall d´Hebron Research Institute)

  • Núria Martínez-Gil

    (Vall d´Hebron Research Institute)

  • Diana Valverde

    (SERGASUVIGO)

  • Carlos Solarat

    (SERGASUVIGO)

  • Ange-Line Buel

    (University of Burgundy)

  • Cristel Thauvin-Robinet

    (University of Burgundy)

  • Elisabeth Steichen

    (University of Innsbruck)

  • Isabel Filges

    (University Hospital Basel)

  • Pascal Joset

    (University Hospital Basel)

  • Julie Geyter

    (University Hospital Basel)

  • Krishna Vaidyanathan

    (University of Texas at Austin)

  • Tynan P. Gardner

    (University of Texas at Austin)

  • Michinori Toriyama

    (Sanda)

  • Edward M. Marcotte

    (University of Texas at Austin)

  • Kevin Drew

    (University of Illinois at Chicago)

  • Elle C. Roberson

    (CU Anschutz Medical Campus)

  • Peter K. Jackson

    (Stanford University School of Medicine)

  • Jeremy F. Reiter

    (San Francisco)

  • Eduardo F. Tizzano

    (Vall d´Hebron Research Institute)

  • John B. Wallingford

    (University of Texas at Austin)

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.

Suggested Citation

  • 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 & Núri, 2025. "The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61005-8
    DOI: 10.1038/s41467-025-61005-8
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