Functional genomics of the cilium, a sensory organelle
Functional genomics of the cilium, a sensory organelle
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DOI：
10.1016/j.cub.2005.04.059
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发表时间：
2005-05-24
期刊：
影响因子：
9.2
通讯作者：
Leroux, MR
中科院分区：
文献类型：
--
作者：
Blacque, OE;Perens, EA;Leroux, MR
纤毛和鞭毛在细胞和体液运动、感觉知觉和发育等许多生理过程中起着重要作用。纤毛的生物发生和维持依赖于纤束内运输（IFT），这是一个沿纤毛轴突双向运行的运动过程[1,2]。IFT和纤毛功能的破坏会导致多种人类疾病，包括多囊肾、视网膜营养不良、神经感觉障碍和Bardet-Bledl综合征（BBS）[3-5]。为了揭示新的纤毛成分，包括IFT蛋白，我们通过基因表达序列分析（SAGE）比较了秀丽隐杆线虫纤毛神经元和非纤毛细胞，并筛选了可能受纤毛转录因子DAF-19[6]调控的基因。利用这些互补的方法，我们鉴定了许多候选纤毛基因，并确认了14个新基因的纤毛细胞特异性表达。其中的C27H5.7a编码一种经历IFT的纤毛蛋白。与其他IFT蛋白一样，它的纤毛定位和运输被IFT和bbs基因的突变破坏。此外，我们证明秀丽隐杆线虫dyf-13（mn396）突变体的纤毛结构缺陷是由C27H5.7a突变引起的。总之，我们的发现有助于定义纤毛转录组，并表明DYF-13（一种进化上保守的蛋白）是纤毛功能所需的新型核心IFT成分。
Cilia and flagella play important roles in many physiological processes, including cell and fluid movement, sensory perception, and development [1]. The biogenesis and maintenance of cilia depend on intraflagellar transport (IFT), a motility process that operates bidirectionally along the ciliary axoneme [1, 2]. Disruption in IFT and cilia function causes several human disorders, including polycystic kidneys, retinal dystrophy, neurosensory impairment, and Bardet-Bledl syndrome (BBS) [3-5]. To uncover new ciliary components, including IFT proteins, we compared C. elegans ciliated neuronal and nonciliated cells through serial analysis of gene expression (SAGE) and screened for genes potentially regulated by the cillogenic transcription factor, DAF-19 [6]. Using these complementary approaches, we identified numerous candidate ciliary genes and confirmed the ciliated-cell-specific expression of 14 novel genes. One of these, C27H5.7a, encodes a ciliary protein that undergoes IFT. As with other IFT proteins, its ciliary localization and transport is disrupted by mutations in IFT and bbs genes. Furthermore, we demonstrate that the ciliary structural defect of C. elegans dyf-13(mn396) mutants is caused by a mutation in C27H5.7a. Together, our findings help define a ciliary transcriptome and suggest that DYF-13, an evolutionarily conserved protein, is a novel core IFT component required for cilia function.