The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery.
Michinori ToriyamaChanjae LeeS Paige TaylorIvan DuranDaniel H CohnAnge-Line BruelJacqueline M TablerKevin DrewMarcus R KellySukyoung KimTae-Joo ParkDaniela A BraunGhislaine PierquinArmand BiverKerstin WagnerAnne MalfrootInusha PanigrahiBrunella FrancoHadeel Adel Al-LamiYvonne YeungYeon Ja Choinull nullYannis DuffourdLaurence FaivreJean-Baptiste RivièreJiang ChenKaren J LiuEdward M MarcotteFriedhelm HildebrandtChristel Thauvin-RobinetDeborah KrakowPeter K JacksonJohn B WallingfordPublished in: Nature genetics (2016)
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.
Keyphrases
- endothelial cells
- genome wide
- end stage renal disease
- newly diagnosed
- induced pluripotent stem cells
- chronic kidney disease
- ejection fraction
- mass spectrometry
- high resolution
- pluripotent stem cells
- peritoneal dialysis
- prognostic factors
- gene expression
- regulatory t cells
- dna methylation
- stem cells
- mesenchymal stem cells
- dendritic cells
- patient reported outcomes
- neural network
- network analysis
- transcription factor
- genome wide analysis