Caenorhabditis elegans DYF-2, an orthologue of human WDR19, is a component of the intraflagellar transport machinery in sensory Cilia
Caenorhabditis elegans DYF-2, an orthologue of human WDR19, is a component of the intraflagellar transport machinery in sensory Cilia
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DOI：
10.1091/mbc.e06-04-0260
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发表时间：
2006-11-01
影响因子：
3.3
通讯作者：
Swoboda, Peter
中科院分区：
文献类型：
--
作者：
Efimenko, Evgeni;Blacque, Oliver E.;Swoboda, Peter
构建功能性纤毛所需的鞭毛内运输（IFT）机制由多亚基复合体组成，其分子组成、组织和功能尚不清楚。在这里，我们描述了一种新型色氨酸-天冬氨酸（WD）重复序列（WDR），含有来自秀丽隐杆线虫的IFT蛋白DYF-2，它在维持IFT机制的结构和功能完整性方面发挥着关键作用。我们通过突变表型的转基因拯救和突变等位基因的测序确定了 dyf-2 基因的身份。 DYF-2功能的丧失选择性地影响不同IFT组件的组装和运动，并导致线虫纤毛结构和化学感觉的缺陷。基于这些观察结果，以及对 IFT 颗粒部分破坏的 Bardet-Biedl 综合征突变体中 DYF-2 运动的分析，我们得出结论，DYF-2 可以与 IFT 颗粒复合物 B 结合。同时，dyf-2 的突变可以干扰复合物 A 组分的功能，表明该蛋白在 IFT 颗粒整体组装中发挥重要作用。重要的是，DYF-2 的小鼠直系同源物 WDR19 也定位于纤毛，表明该 WDR 蛋白在纤毛发育和功能中具有重要的进化保守作用。
The intraflagellar transport (IFT) machinery required to build functional cilia consists of a multisubunit complex whose molecular composition, organization, and function are poorly understood. Here, we describe a novel tryptophan-aspartic acid (WD) repeat (WDR) containing IFT protein from Caenorhabditis elegans, DYF-2, that plays a critical role in maintaining the structural and functional integrity of the IFT machinery. We determined the identity of the dyf-2 gene by transgenic rescue of mutant phenotypes and by sequencing of mutant alleles. Loss of DYF-2 function selectively affects the assembly and motility of different IFT components and leads to defects in cilia structure and chemosensation in the nematode. Based on these observations, and the analysis of DYF-2 movement in a Bardet-Biedl syndrome mutant with partially disrupted IFT particles, we conclude that DYF-2 can associate with IFT particle complex B. At the same time, mutations in dyf-2 can interfere with the function of complex A components, suggesting an important role of this protein in the assembly of the IFT particle as a whole. Importantly, the mouse orthologue of DYF-2, WDR19, also localizes to cilia, pointing to an important evolutionarily conserved role for this WDR protein in cilia development and function.