Intraflagellar transport protein IFT52 recruits IFT46 to the basal body and flagella
Intraflagellar transport protein IFT52 recruits IFT46 to the basal body and flagella
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鞭毛内转运蛋白 IFT52 将 IFT46 招募到基体和鞭毛
DOI：
10.1242/jcs.200758
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发表时间：
2017-05-01
影响因子：
4
通讯作者：
Huang, Kaiyao
中科院分区：
文献类型：
--
作者：
Lv, Bo;Wan, Lei;Huang, Kaiyao
纤毛是基于微管的细胞器，具有运动、传感和信号功能。纤毛的组装和维持依赖于鞭毛内运输（IFT）。除了纤毛定位外，大多数IFT蛋白都聚集在基底体。然而，对于IFT蛋白基底体靶向的分子机制知之甚少。我们首先通过在IFT46 -1突变体中表达IFT46截断构建体，确定了IFT46中可能的基础体靶向序列。在ift46-1菌株中，残基246-321之间的c端序列被称为BBTS3，足以将YFP靶向到基体上。有趣的是，BBTS3也负责IFT46的纤毛靶向。BBTS3: YFP在鞭毛中双向移动，并与其他IFT复合物B （IFT-B）蛋白相互作用。利用IFT和运动突变体，我们发现IFT46的基础体定位依赖于IFT52，而不依赖于IFT81、IFT88、IFT122、FLA10或DHC1b。IFT52通过IFT46的L285和L286残基与IFT46相互作用，并将其招募到基底体。细胞核中IFT52 c端结构域的异位表达导致IFT46在细胞核中积累。这些数据表明IFT52和IFT46可以在细胞质中作为复合物预先组装，然后靶向基底体。摘要：我们确定了IFT46中负责其基底和纤毛定位的区域。该序列促进与IFT52的相互作用，IFT52将IFT46招募到基础体。
ABSTRACT Cilia are microtubule-based organelles and perform motile, sensing and signaling functions. The assembly and maintenance of cilia depend on intraflagellar transport (IFT). Besides ciliary localization, most IFT proteins accumulate at basal bodies. However, little is known about the molecular mechanism of basal body targeting of IFT proteins. We first identified the possible basal body-targeting sequence in IFT46 by expressing IFT46 truncation constructs in an ift46-1 mutant. The C-terminal sequence between residues 246–321, termed BBTS3, was sufficient to target YFP to basal bodies in the ift46-1 strain. Interestingly, BBTS3 is also responsible for the ciliary targeting of IFT46. BBTS3::YFP moves bidirectionally in flagella and interacts with other IFT complex B (IFT-B) proteins. Using IFT and motor mutants, we show that the basal body localization of IFT46 depends on IFT52, but not on IFT81, IFT88, IFT122, FLA10 or DHC1b. IFT52 interacts with IFT46 through residues L285 and L286 of IFT46 and recruits it to basal bodies. Ectopic expression of the C-terminal domain of IFT52 in the nucleus resulted in accumulation of IFT46 in nuclei. These data suggest that IFT52 and IFT46 can preassemble as a complex in the cytoplasm, which is then targeted to basal bodies. Summary: We identify the region in IFT46 that is responsible for its basal body and ciliary localization. This sequence promotes interaction with IFT52, which recruits IFT46 to the basal body.