Dataset Information

Mouse ciliopathy-associated CPLANE proteins

ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap Velos, LTQ Orbitrap XL

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Inner Medullary Collecting Duct

DISEASE(S): Disease Free

SUBMITTER: Janos Demeter

LAB HEAD: Peter K. Jackson

PROVIDER: PXD004741 | Pride | 2016-08-15

REPOSITORIES: Pride

ACCESS DATA

Publications

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

Toriyama Michinori M Lee Chanjae C Taylor S Paige SP Duran Ivan I Cohn Daniel H DH Bruel Ange-Line AL Tabler Jacqueline M JM Drew Kevin K Kelly Marcus R MR Kim Sukyoung S Park Tae Joo TJ Braun Daniela A DA Pierquin Ghislaine G Biver Armand A Wagner Kerstin K Malfroot Anne A Panigrahi Inusha I Franco Brunella B Al-Lami Hadeel Adel HA Yeung Yvonne Y Choi Yeon Ja YJ Duffourd Yannis Y Faivre Laurence L Rivière Jean-Baptiste JB Chen Jiang J Liu Karen J KJ Marcotte Edward M EM Hildebrandt Friedhelm F Thauvin-Robinet Christel C Krakow Deborah D Jackson Peter K PK Wallingford John B JB

Nature genetics 20160509 6

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 ...[more]

PMID: 27158779

Similar Datasets

Project description:Study Smoking and COPD are associated with decreased mucociliary clearance and healthy smokers have shorter cilia in the large airway than nonsmokers. Intraflagellar transport (IFT) is the process by which cilia are produced and maintained. We assessed expression of IFT-related genes in smokers and nonsmokers and evaluated cilia length in the large and small airway of nonsmokers, healthy smokers, and smokers with COPD. Methods Airway epithelium was obtained via bronchoscopic brushing. Affymetrix microarrays were used to evaluate IFT gene expression in 2 independent data sets from large and small airway. Cilia length was assessed by measuring 100 cilia (10 cilia on each of 10 cells) per subject. Results All 40 IFT genes were expressed in the human large and small airway epithelium. In the large airway, 10 IFT genes were down-regulated and 1 up-regulated in smokers. In the small airway, 11 genes were down-regulated and 3 up-regulated in smokers. A set of 8 IFT genes was down-regulated in both data sets. In the large and small airway epithelium, cilia were significantly shorter in healthy smokers than nonsmokers, and significantly shorter in COPD smokers than in both healthy smokers and nonsmokers. Answer to the Question These results support the concept that loss of cilia length contributes to defective mucociliary clearance in COPD, and that smoking-induced changes in expression of IFT genes may be one mechanism of abnormally short cilia in smokers. Strategies to normalize cilia length may be an important avenue for novel COPD therapies. Gene expression was assessed for 40 intraflagellar transport related genes in the LAE of nonsmokers (n=21) and healthy smokers (n=31) and the SAE of an independent group of nonsmokers (n=28) and healthy smokers (n=69). Cilia length was assessed in a total of 228 airway epithelium samples, including 120 LAE samples and 108 SAE samples; a subset of the 228 samples is represented among the 149 samples in this Series.

Dataset Information

Mouse ciliopathy-associated CPLANE proteins

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure