The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery
Michinori Toriyama
(1)
,
Chanjae Lee
(1)
,
S Paige Taylor
(2)
,
Ivan Duran
(3)
,
Daniel H Cohn
(4)
,
Ange-Line Bruel
(5, 6)
,
Jacqueline M Tabler
(1)
,
Kevin Drew
(1)
,
Marcus R Kelly
(7)
,
Sukyoung Kim
(1)
,
Tae Joo Park
(8, 1)
,
Daniela A Braun
(9)
,
Ghislaine Pierquin
(10)
,
Armand Biver
(11)
,
Kerstin Wagner
(12)
,
Anne Malfroot
(13)
,
Inusha Panigrahi
(14)
,
Brunella Franco
(15)
,
Hadeel Adel Al-Lami
(16)
,
Yvonne Yeung
(16)
,
Yeon Ja Choi
(17)
,
Yannis Duffourd
(5)
,
Laurence Faivre
(5, 6)
,
Jean-Baptiste Rivière
(5)
,
Jiang Chen
(17)
,
Karen J Liu
(16)
,
Edward M Marcotte
(1)
,
Friedhelm Hildebrandt
(9)
,
Christel Thauvin-Robinet
(5, 6)
,
Deborah Krakow
(4)
,
Peter K Jackson
(7)
,
John B Wallingford
(1)
1
Department of Molecular Biosciences
2 Departement of human genetics [Los Angeles]
3 David Geffen School of Medicine [Los Angeles]
4 Department of Molecular Cellular and Developmental Biology
5 GAD - Génétique des Anomalies du Développement
6 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)
7 Department of Microbiology and Immunology [Stanford]
8 Division of Polar Earth-System Sciences
9 HHMI - Howard Hughes Medical Institute [Chevy Chase]
10 Centre de Génétique Humaine
11 Département de Génétique, CHU, Liège
12 KannerKlinik Pédiatrie générale
13 Units of Pediatric Pulmonology
14 PGIMER - Advanced Pediatric Center
15 Dipartimento di Scienze Mediche Traslazionali
16 LDI - London Dental Institute
17 SUNY - State University of New York
2 Departement of human genetics [Los Angeles]
3 David Geffen School of Medicine [Los Angeles]
4 Department of Molecular Cellular and Developmental Biology
5 GAD - Génétique des Anomalies du Développement
6 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)
7 Department of Microbiology and Immunology [Stanford]
8 Division of Polar Earth-System Sciences
9 HHMI - Howard Hughes Medical Institute [Chevy Chase]
10 Centre de Génétique Humaine
11 Département de Génétique, CHU, Liège
12 KannerKlinik Pédiatrie générale
13 Units of Pediatric Pulmonology
14 PGIMER - Advanced Pediatric Center
15 Dipartimento di Scienze Mediche Traslazionali
16 LDI - London Dental Institute
17 SUNY - State University of New York
John B Wallingford
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Résumé
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.