TALPID3 and ANKRD26 selectively orchestrate FBF1 localization and cilia gating
TALPID3 and ANKRD26 selectively orchestrate FBF1 localization and cilia gating
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TALPID3 和 ANKRD26 选择性地协调 FBF1 定位和纤毛门控
DOI：
10.1038/s41467-020-16042-w
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发表时间：
2020
影响因子：
16.6
通讯作者：
Wei Qing
中科院分区：
文献类型：
--
作者：
Yan Hao;Chen Chuan;Chen Huicheng;Hong Hui;Huang Yan;Ling Kun;Hu Jinghua;Wei Qing
过渡纤维调节纤毛门控，使初级纤毛成为一个独特的功能实体。然而，对功能纤毛门的生物发生的分子洞察仍然难以捉摸。在秀丽隐杆线虫的正向遗传筛查中，我们发现TALP-3是Joubert综合征蛋白TALPID3的同源物，是一种与TF相关的成分。遗传分析表明，TALP-3与ANKRD26的同源物ANKR-26配位，以协调适当的纤毛门控。从机械上讲，TALP-3和ANKR-26与关键的门控组件DYF-19形成了复合体，DYF-19是FBF1的同系物。TALP-3和ANKR-26的共同消耗具体损害了DYF-19向部队的招募。有趣的是，在哺乳动物细胞中，TALPID3和ANKRD26也在协调FBF1到TF的招募方面发挥着保守的作用。因此，我们报告了一个保守的蛋白质模块，该模块专门调节睫状门的功能成分，并提示有缺陷的门控与纤毛疾病的发病机制之间存在相关性。
Transition fibers (TFs) regulate cilia gating and make the primary cilium a distinct functional entity. However, molecular insights into the biogenesis of a functional cilia gate remain elusive. In a forward genetic screen inCaenorhabditis elegans, we uncover that TALP-3, a homolog of the Joubert syndrome protein TALPID3, is a TF-associated component. Genetic analysis reveals that TALP-3 coordinates with ANKR-26, the homolog of ANKRD26, to orchestrate proper cilia gating. Mechanistically, TALP-3 and ANKR-26 form a complex with key gating component DYF-19, the homolog of FBF1. Co-depletion of TALP-3 and ANKR-26 specifically impairs the recruitment of DYF-19 to TFs. Interestingly, in mammalian cells, TALPID3 and ANKRD26 also play a conserved role in coordinating the recruitment of FBF1 to TFs. We thus report a conserved protein module that specifically regulates the functional component of the ciliary gate and suggest a correlation between defective gating and ciliopathy pathogenesis.