The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery.
The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery.
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DOI：
10.1038/ng.3558
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发表时间：
2016-06
期刊：
影响因子：
30.8
通讯作者：
Wallingford JB
中科院分区：
文献类型：
--
作者：
Toriyama M;Lee C;Taylor SP;Duran I;Cohn DH;Bruel AL;Tabler JM;Drew K;Kelly MR;Kim S;Park TJ;Braun DA;Pierquin G;Biver A;Wagner K;Malfroot A;Panigrahi I;Franco B;Al-Lami HA;Yeung Y;Choi YJ;University of Washington Center for Mendelian Genomics;Duffourd Y;Faivre L;Rivière JB;Chen J;Liu KJ;Marcotte EM;Hildebrandt F;Thauvin-Robinet C;Krakow D;Jackson PK;Wallingford JB
纤毛利用微管为基础的鞭毛内运输（IFT）组织细胞间的信号。纤毛病是由纤毛结构或功能缺陷引起的一系列人类疾病。调节纤毛多蛋白复合物组装及其运输到纤毛基部的机制在很大程度上仍然未知。结合联合收割机蛋白质组学、体内成像和与平面细胞极性相关的蛋白质的遗传分析（反转、模糊、WDPCP），我们鉴定并表征了一个新的遗传模块，我们称之为CPLANE（纤毛发生和平面极性效应器）和一个广泛的相关蛋白质网络。CPLANE蛋白质在基体上与知之甚少的纤毛蛋白Jbts 17在物理和功能上相互作用，在那里它们起作用以招募特定的IFT-A蛋白亚群。在没有CPLANE的情况下，有缺陷的IFT-A颗粒进入轴丝，IFT-B运输受到严重干扰。因此，CPLANE基因突变在小鼠模型中引起特异性纤毛病变表型，并与人类患者中的新型纤毛病变相关。
Cilia use microtubule-based intraflagellar transport (IFT) to organize intercellular signaling. The ciliopathies are a spectrum of human disease resulting from defects in cilia structure or function. Mechanisms regulating assembly of ciliary multiprotein complexes and their transport to the base of cilia remain largely unknown. Combine proteomics, in vivo imaging, and genetic analysis of proteins linked to planar cell polarity (Inturned, Fuzzy, 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 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 novel ciliopathies in human patients.