Qilin is essential for cilia assembly and normal kidney development in zebrafish.
Qilin is essential for cilia assembly and normal kidney development in zebrafish.
复制标题
DOI：
10.1371/journal.pone.0027365
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Sun Z
中科院分区：
文献类型：
--
作者：
Li J;Sun Z
纤毛缺陷，一种曾经被认为是退化的细胞器，最近被认为与许多人类疾病有关，包括许多囊性肾病，如多囊性肾病（PKD）， Bardet Bieldl综合征和Meckel-Gruber综合征。在正向遗传筛选中，麒麟基因被鉴定为在斑马鱼肾囊肿发病机制中起重要作用的新基因。本文详细描述了qilinhi3959A突变体的表型，研究了该突变体的纤毛形成，并对其进行了结构和功能分析。结果表明，麒麟在包括肾脏、侧线器官和感光细胞外段在内的多个器官的纤毛组装和维持中起重要作用。此外，救援实验表明，在qilinhi3959A突变体中，肾原纤毛缺陷与肾囊肿的形成有关。此外，遗传分析表明，麒琳与多个IFT复合物B基因相互作用，这得到了qilinhi3959A和IFT复合物B突变体之间惊人的表型相似性的支持。最后，通过缺失分析，我们提供了证据，证明麒麟基因的n端和盘绕盘绕结构域是其功能的必要和充分条件。综上所述，我们认为麒麟蛋白在斑马鱼纤毛组装、维持和肾脏发育中的作用与IFT复合物B蛋白相似。
Defects in the cilium, a once thought vestigial organelle, have recently been implicated in many human diseases, including a number of cystic kidney diseases such as polycystic kidney disease (PKD), Bardet Bieldl Syndrome, and Meckel-Gruber Syndrome. In a forward genetic screen, qilin was identified as a novel gene important in the pathogenesis of kidney cysts in zebrafish. In this paper we characterized qilinhi3959A mutant's phenotypes in detail, investigated cilia formation in this mutant and performed structural and functional analysis of the Qilin protein. Results reveal Qilin's essential role in cilia assembly and maintenance in multiple organs, including the kidney, the lateral line organ, and the outer segment of the photoreceptor cell. In addition, rescue experiments suggest that defective pronephric cilia correlate with the formation of kidney cysts in qilinhi3959A mutants. Further, genetic analysis suggests that qilin interacts with multiple intraflagellar transport (IFT) complex B genes, which is supported by the striking phenotypic similarities between qilinhi3959A and IFT complex B mutants. Finally, through deletion analysis we provide evidence that the well-conserved N-terminus and the coiled-coil domain of Qilin are both essential and sufficient for its function. Taken all the observations together, we propose that Qilin acts in a similar role as IFT complex B proteins in cilia assembly, maintenance and kidney development in zebrafish.
登录
查看更多内容
影响因子：
7.8
作者：
Pazour, GJ;Wilkerson, CG;Witman, GB
通讯作者：
Witman, GB
影响因子：
4.5
作者：
Ma, Ming;Jiang, Yun-Jin
通讯作者：
Jiang, Yun-Jin
影响因子：
4
作者：
Eley, L;Yates, LM;Goodship, JA
通讯作者：
Goodship, JA
影响因子：
21.3
作者：
Omori, Yoshihiro;Zhao, Chengtian;Malicki, Jarema
通讯作者：
Malicki, Jarema
DOI：
10.1083/jcb.141.4.993
发表时间：
1998-05-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Cole DG;Diener DR;Himelblau AL;Beech PL;Fuster JC;Rosenbaum JL
通讯作者：
Rosenbaum JL