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Nat Genet. 2016 Jun;48(6):648-56. doi: 10.1038/ng.3558. Epub 2016 May 9.

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

Author information

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

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.

PMID:
27158779
PMCID:
PMC4978421
DOI:
10.1038/ng.3558
[PubMed - in process]
Free PMC Article
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