title: The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery.
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.
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.
authors.forename: Michinori
authors.initials: M
authors.lastname: Toriyama
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.
authors.forename: Chanjae
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.|Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.|Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: S Paige
authors.initials: SP
authors.lastname: Taylor
authors.affiliation: Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.|Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.|Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Ivan
authors.identifier: 0000-0001-6097-0402
authors.initials: I
authors.lastname: Duran
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Cohn
authors.affiliation: EA4271GAD Genetics of Developmental Anomalies, FHU-TRANSLAD, Medecine Faculty, Burgundy University, Dijon, France.
authors.forename: Ange-Line
authors.initials: AL
authors.lastname: Bruel
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Tabler
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Drew
authors.affiliation: Baxter Laboratory, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Marcus R
authors.initials: MR
authors.lastname: Kelly
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.
authors.forename: Sukyoung
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.
authors.forename: Tae Joo
authors.identifier: 0000-0003-3176-177X
authors.initials: TJ
authors.lastname: Park
authors.affiliation: Howard Hughes Medical Institute, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.|Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Daniela A
authors.initials: DA
authors.lastname: Braun
authors.affiliation: Clinical Genetics Centre, University Hospital Center, Liège, Belgium.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Pierquin
authors.affiliation: Pediatric Unit, Hospital Center, Luxemburg, Luxembourg.
authors.forename: Armand
authors.initials: A
authors.lastname: Biver
authors.affiliation: Cardiological Pediatric Unit, Hospital Center, Luxemburg, Luxembourg.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wagner
authors.affiliation: Clinic of Pediatric Respiratory Diseases, Universitair Ziekenhuis Brussel, Brussels, Belgium.|Infectious Diseases, Travel Clinic, Universitair Ziekenhuis Brussel, Brussels, Belgium.|Cystic Fibrosis Clinic, Universitair Ziekenhuis Brussel, Brussels, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Malfroot
authors.affiliation: Department of Pediatrics Advanced, Pediatric Centre Pigmer, Chandigarh, India.
authors.forename: Inusha
authors.initials: I
authors.lastname: Panigrahi
authors.affiliation: Division of Pediatrics, Department of Medical Translational Sciences, Federico II University of Naples, Naples, Italy.|Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
authors.forename: Brunella
authors.initials: B
authors.lastname: Franco
authors.affiliation: Department of Craniofacial and Stem Cell Biology, Dental Institute, King's College London, London, UK.
authors.forename: Hadeel Adel
authors.identifier: 0000-0003-1255-3481
authors.initials: HA
authors.lastname: Al-Lami
authors.affiliation: Department of Craniofacial and Stem Cell Biology, Dental Institute, King's College London, London, UK.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Yeung
authors.affiliation: Department of Pathology, Stony Brook University, Stony Brook, New York, USA.|Department of Dermatology, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Yeon Ja
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: EA4271GAD Genetics of Developmental Anomalies, FHU-TRANSLAD, Medecine Faculty, Burgundy University, Dijon, France.
authors.forename: Yannis
authors.initials: Y
authors.lastname: Duffourd
authors.affiliation: EA4271GAD Genetics of Developmental Anomalies, FHU-TRANSLAD, Medecine Faculty, Burgundy University, Dijon, France.|Clinical Genetics Centre, FHU-TRANSLAD, Children Hospital, CHU Dijon, Dijon, France.|Eastern Referral Centre for Developmental Anomalies and Malformative Syndromes, FHU-TRANSLAD, Children Hospital, CHU Dijon, Dijon, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.affiliation: EA4271GAD Genetics of Developmental Anomalies, FHU-TRANSLAD, Medecine Faculty, Burgundy University, Dijon, France.|Laboratory of Molecular Genetics, FHU-TRANSLAD, PTB, CHU Dijon, Dijon, France.
authors.forename: Jean-Baptiste
authors.identifier: 0000-0001-9144-4210
authors.initials: JB
authors.lastname: Rivière
authors.affiliation: Department of Pathology, Stony Brook University, Stony Brook, New York, USA.|Department of Dermatology, Stony Brook University, Stony Brook, New York, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Craniofacial and Stem Cell Biology, Dental Institute, King's College London, London, UK.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Liu
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Marcotte
authors.affiliation: Howard Hughes Medical Institute, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.|Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
authors.affiliation: EA4271GAD Genetics of Developmental Anomalies, FHU-TRANSLAD, Medecine Faculty, Burgundy University, Dijon, France.|Laboratory of Molecular Genetics, FHU-TRANSLAD, PTB, CHU Dijon, Dijon, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin-Robinet
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Krakow
authors.affiliation: Baxter Laboratory, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Jackson
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.
authors.forename: John B
authors.initials: JB
authors.lastname: Wallingford
mesh_terms: D000818:Animals; D000072661:Ciliopathies / Q000378:metabolism*; D005407:Flagella / Q000502:physiology*; D006801:Humans; D051379:Mice; D009154:Mutation; D010641:Phenotype; D011485:Protein Binding; D021381:Protein Transport; D011506:Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D011506:Proteins