2. Academic Validation
  3. The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery

The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery

  • Nat Genet. 2016 Jun;48(6):648-56. doi: 10.1038/ng.3558.
Michinori Toriyama 1,  Chanjae Lee 1,  S Paige Taylor 2 3 4,  Ivan Duran 2 3 4,  Daniel H Cohn 5,  Ange-Line Bruel 6,  Jacqueline M Tabler 1,  Kevin Drew 1,  Marcus R Kelly 7,  Sukyoung Kim 1,  Tae Joo Park 1,  Daniela A Braun 8 9,  Ghislaine Pierquin 10,  Armand Biver 11,  Kerstin Wagner 12,  Anne Malfroot 13 14 15,  Inusha Panigrahi 16,  Brunella Franco 17 18,  Hadeel Adel Al-Lami 19,  Yvonne Yeung 19,  Yeon Ja Choi 20 21,  University of Washington Center for Mendelian Genomics,  Yannis Duffourd 6,  Laurence Faivre 6 22 23,  Jean-Baptiste Rivière 6 24,  Jiang Chen 20 21,  Karen J Liu 19,  Edward M Marcotte 1,  Friedhelm Hildebrandt 8 9,  Christel Thauvin-Robinet 6 24,  Deborah Krakow 5,  Peter K Jackson 7,  John B Wallingford 1
Affiliations

Affiliations

  • 1 Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.
  • 2 Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
  • 3 Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
  • 4 Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
  • 5 Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California, USA.
  • 6 EA4271GAD Genetics of Developmental Anomalies, FHU-TRANSLAD, Medecine Faculty, Burgundy University, Dijon, France.
  • 7 Baxter Laboratory, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
  • 8 Howard Hughes Medical Institute, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • 9 Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
  • 10 Clinical Genetics Centre, University Hospital Center, Liège, Belgium.
  • 11 Pediatric Unit, Hospital Center, Luxemburg, Luxembourg.
  • 12 Cardiological Pediatric Unit, Hospital Center, Luxemburg, Luxembourg.
  • 13 Clinic of Pediatric Respiratory Diseases, Universitair Ziekenhuis Brussel, Brussels, Belgium.
  • 14 Infectious Diseases, Travel Clinic, Universitair Ziekenhuis Brussel, Brussels, Belgium.
  • 15 Cystic Fibrosis Clinic, Universitair Ziekenhuis Brussel, Brussels, Belgium.
  • 16 Department of Pediatrics Advanced, Pediatric Centre Pigmer, Chandigarh, India.
  • 17 Division of Pediatrics, Department of Medical Translational Sciences, Federico II University of Naples, Naples, Italy.
  • 18 Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
  • 19 Department of Craniofacial and Stem Cell Biology, Dental Institute, King's College London, London, UK.
  • 20 Department of Pathology, Stony Brook University, Stony Brook, New York, USA.
  • 21 Department of Dermatology, Stony Brook University, Stony Brook, New York, USA.
  • 22 Clinical Genetics Centre, FHU-TRANSLAD, Children Hospital, CHU Dijon, Dijon, France.
  • 23 Eastern Referral Centre for Developmental Anomalies and Malformative Syndromes, FHU-TRANSLAD, Children Hospital, CHU Dijon, Dijon, France.
  • 24 Laboratory of Molecular Genetics, FHU-TRANSLAD, PTB, CHU Dijon, Dijon, France.
PMID: 27158779 DOI: 10.1038/ng.3558
Abstract

Cilia use microtubule-based intraflagellar transport (IFT) to organize intercellular signaling. Ciliopathies are a spectrum of human diseases resulting from defects in cilia structure or function. The mechanisms regulating the assembly of ciliary multiprotein complexes and the transport of these complexes to the base of cilia remain largely unknown. Combining proteomics, in vivo imaging and genetic analysis of proteins linked to planar cell polarity (Inturned, Fuzzy and Wdpcp), we identified and characterized a new genetic module, which we term CPLANE (ciliogenesis and planar polarity effector), and an extensive associated protein network. CPLANE proteins physically and functionally interact with the poorly understood ciliopathy-associated protein Jbts17 at basal bodies, where they act to recruit a specific subset of IFT-A proteins. In the absence of CPLANE, defective IFT-A particles enter the axoneme and IFT-B trafficking is severely perturbed. Accordingly, mutation of CPLANE genes elicits specific ciliopathy phenotypes in mouse models and is associated with ciliopathies in human patients.

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