Toriyama Michinori, Lee Chanjae, Taylor S Paige, Duran Ivan, Cohn Daniel H, Bruel Ange-Line, Tabler Jacqueline M, Drew Kevin, Kelly Marcus R, Kim Sukyoung, Park Tae Joo, Braun Daniela A, Pierquin Ghislaine, Biver Armand, Wagner Kerstin, Malfroot Anne, Panigrahi Inusha, Franco Brunella, Al-Lami Hadeel Adel, Yeung Yvonne, Choi Yeon Ja, Duffourd Yannis, Faivre Laurence, Rivière Jean-Baptiste, Chen Jiang, Liu Karen J, Marcotte Edward M, Hildebrandt Friedhelm, Thauvin-Robinet Christel, Krakow Deborah, Jackson Peter K, Wallingford John B
Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.
Department of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Nat Genet. 2016 Jun;48(6):648-56. doi: 10.1038/ng.3558. Epub 2016 May 9.
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.
纤毛利用基于微管的鞭毛内运输（IFT）来组织细胞间信号传导。纤毛病是由纤毛结构或功能缺陷导致的一系列人类疾病。调节纤毛多蛋白复合物组装以及这些复合物向纤毛基部运输的机制在很大程度上仍然未知。通过结合蛋白质组学、体内成像以及对与平面细胞极性相关蛋白质（内翻蛋白、模糊蛋白和Wdpcp）的遗传分析，我们鉴定并表征了一个新的遗传模块，我们将其命名为CPLANE（纤毛发生和平面极性效应器）以及一个广泛的相关蛋白质网络。CPLANE蛋白在基体处与了解较少的纤毛病相关蛋白Jbts17发生物理和功能相互作用，在那里它们起到招募IFT-A蛋白特定亚群的作用。在没有CPLANE的情况下，有缺陷的IFT-A颗粒进入轴丝，并且IFT-B运输受到严重干扰。因此，CPLANE基因的突变在小鼠模型中引发特定的纤毛病表型，并且与人类患者的纤毛病相关。
