Caenorhabditis elegans DYF-11, an orthologue of mammalian Traf3ip1/MIP-T3, is required for sensory cilia formation
Caenorhabditis elegans DYF-11, an orthologue of mammalian Traf3ip1/MIP-T3, is required for sensory cilia formation
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DOI：
10.1111/j.1365-2443.2007.01147.x
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发表时间：
2008-01-01
期刊：
影响因子：
2.1
通讯作者：
Iino, Yuichi
中科院分区：
文献类型：
--
作者：
Kunitomo, Hirofumi;Iino, Yuichi
纤毛和鞭毛在动物的细胞运动、发育和感觉知觉中起着关键作用。纤毛的形成和维持需要一个保守的蛋白质转运系统，称为鞭毛内转运（IFT）。在这里，我们表明，秀丽隐杆线虫dyf-11编码的纤毛生物发生所需的进化保守的蛋白质。dyf-11在大多数纤毛神经元中表达，并受C.优雅的dyf-11突变体表现出纤毛发育不良、感觉神经元的荧光染料填充缺陷（Dyf）和异常趋化性（Che）。细胞和阶段特异性拯救实验表明，DYF-11是细胞自主方式的感觉纤毛的形成和维持所必需的。荧光蛋白标记的DYF-11定位于纤毛，并通过IFT向前和向后移动。对bbs突变体中DYF-11运动的分析进一步表明DYF-11可能与IFT复合物B相关。使用DYF-11缺失构建体的结构域分析表明，卷曲螺旋区域是正确定位和纤毛发生所需的。我们进一步表明，TRAF 3 ip 1/MIP-T3，DYF-11的哺乳动物直向同源物，定位于MDCK肾上皮细胞的纤毛。
Cilia and flagella play critical roles in cell motility, development and sensory perception in animals. Formation and maintenance of cilia require a conserved protein transport system called intraflagellar transport (IFT). Here, we show that Caenorhabditis elegans dyf-11 encodes an evolutionarily conserved protein required for cilium biogenesis. dyf-11 is expressed in most of the ciliated neurons and is regulated by DAF-19, a crucial transcription factor for ciliary genes in C. elegans. dyf-11 mutants exhibit stunted cilia, fluorescent dye-filling defects (Dyf) of sensory neurons, and abnormal chemotaxis (Che). Cell- and stage-specific rescue experiments indicated that DYF-11 is required for formation and maintenance of sensory cilia in cell-autonomous manner. Fluorescent protein-tagged DYF-11 localizes to cilia and moves antero- and retrogradely via IFT. Analysis of DYF-11 movement in bbs mutants further suggested that DYF-11 is likely associated with IFT complex B. Domain analysis using DYF-11 deletion constructs revealed that the coiled-coil region is required for proper localization and ciliogenesis. We further show that Traf3ip1/MIP-T3, the mammalian orthologue of DYF-11, localizes to cilia in the MDCK renal epithelial cells.