TTC26/DYF13 is an intraflagellar transport protein required for transport of motility-related proteins into flagella.
TTC26/DYF13 is an intraflagellar transport protein required for transport of motility-related proteins into flagella.
复制标题
TTC26/DYF13是将与运动相关蛋白转运到鞭毛所需的flagellar内转运蛋白。
DOI：
10.7554/elife.01566
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发表时间：
2014-01-01
期刊：
影响因子：
7.7
通讯作者：
Marshall WF
中科院分区：
文献类型：
--
作者：
Ishikawa H;Ide T;Yagi T;Jiang X;Hirono M;Sasaki H;Yanagisawa H;Wemmer KA;Stainier DY;Qin H;Kamiya R;Marshall WF
纤毛/鞭毛通过鞭毛内转运（IFT）过程组装和维持，这是一种高度保守的机制，涉及20多种IFT蛋白。然而，单个IFT蛋白的功能大多不清楚。为了帮助解决这个问题，我们专注于一个假定的IFT蛋白TTC 26/DYF 13。利用活体成像和生物化学方法，我们表明，TTC 26/DYF 13是一个IFT复杂的B蛋白在哺乳动物细胞和莱茵衣藻。斑马鱼胚胎中TTC 26/DYF 13的敲除或C.中TTC 26/DYF 13的突变reinhardtii，产生短纤毛，运动异常。令人惊讶的是，IFT颗粒组装和速度是正常的dyf 13突变体鞭毛，不像在其他IFT复合物B突变体。蛋白质组学和生物化学分析表明，dyf 13突变体中参与运动的一组特定蛋白质被特异性耗尽。这些结果支持了不同IFT蛋白负责不同货物子集的概念，为IFT机制的复杂性提供了可能的解释。http://dx.doi.org/10.7554/eLife.01566.001精子细胞有一条叫做鞭毛的尾巴，可以把它们推向卵子。其他细胞也有类似的，但更短的，称为纤毛的结构，在它们的表面来回摆动。除了将灰尘和碎片从我们的肺部和呼吸道中清除外，纤毛在发育过程中还有许多其他关键作用。这意味着有缺陷的纤毛会导致严重的出生缺陷，以及肾脏和呼吸系统疾病。纤毛和鞭毛是由蛋白质组成的，这些蛋白质在一个称为鞭毛内运输或IFT的过程中组装而成。大约有20种蛋白质被认为参与了这一过程，但其中许多蛋白质的确切作用仍不清楚。现在，石川等人已经比较了这些蛋白质中一种叫做TTC 26的蛋白质的版本，这种蛋白质存在于斑马鱼、小鼠细胞和一种叫做莱茵衣藻的单细胞生物中，这种单细胞生物使用一对鞭毛四处移动。该蛋白定位于小鼠细胞的纤毛，并且可以看到以其他IFT蛋白的典型方式沿着这些纤毛沿着移动。石川等人随后阻断了斑马鱼胚胎中TTC 26的产生，导致这些胚胎无法发育出正确的左右不对称，这些鱼的眼睛、耳朵和肾脏也出现了问题。此外，虽然纤毛存在于受影响的斑马鱼，这些纤毛缩短和移动异常。石川等人还发现，编码TTC 26的基因发生突变的藻类具有以异常方式移动的短纤毛。石川等人的研究结果表明，TTC 26可能有助于将特定的蛋白质亚群转运到纤毛中。如果其他IFT蛋白也显示携带不同的货物子集，这可能解释为什么多达20种不同的蛋白质参与IFT过程。DOI：http://dx.doi.org/10.7554/eLife.01566.002网站
Cilia/flagella are assembled and maintained by the process of intraflagellar transport (IFT), a highly conserved mechanism involving more than 20 IFT proteins. However, the functions of individual IFT proteins are mostly unclear. To help address this issue, we focused on a putative IFT protein TTC26/DYF13. Using live imaging and biochemical approaches we show that TTC26/DYF13 is an IFT complex B protein in mammalian cells and Chlamydomonas reinhardtii. Knockdown of TTC26/DYF13 in zebrafish embryos or mutation of TTC26/DYF13 in C. reinhardtii, produced short cilia with abnormal motility. Surprisingly, IFT particle assembly and speed were normal in dyf13 mutant flagella, unlike in other IFT complex B mutants. Proteomic and biochemical analyses indicated a particular set of proteins involved in motility was specifically depleted in the dyf13 mutant. These results support the concept that different IFT proteins are responsible for different cargo subsets, providing a possible explanation for the complexity of the IFT machinery. DOI: http://dx.doi.org/10.7554/eLife.01566.001 Sperm cells have tails called flagella that propel them towards an egg. Other cells have similar, but shorter, structures called cilia that sway back and forth on their surface. In addition to sweeping dust and debris out of our lungs and airways, cilia have a number of other crucial roles during development. This means that faulty cilia can lead to serious birth defects, as well as diseases of the kidneys and respiratory system. Cilia and flagella are made from proteins that are assembled in a process called intraflagellar transport or IFT for short. Around 20 proteins are thought to be involved in this process, but the precise role of many of these proteins remains unclear. Now Ishikawa et al. have compared the versions of one of these proteins, called TTC26, that are found in zebrafish, mouse cells, and a single-celled alga called Chlamydomonas reinhardtii that uses a pair of flagella to move around. This protein localizes to the cilia of mice cells and can be seen to move along these cilia in a manner typical of other IFT proteins. Ishikawa et al. then blocked production of TTC26 in zebrafish embryos, which caused these embryos to fail to develop the correct left–right asymmetry, and these fish also had problems with their eyes, ears, and kidneys. Furthermore and although cilia were present in the affected zebrafish, these cilia were shortened and moved abnormally. Ishikawa et al. also found that algae that had a mutation in the gene that codes for TTC26 had short cilia that moved in an abnormal way. The findings of Ishikawa et al. suggest that TTC26 may help to transport a specific subset of proteins into the cilia. If other IFT proteins are also shown to carry distinct subsets of cargo, this might explain why as many as 20 different proteins are involved in the IFT process. DOI: http://dx.doi.org/10.7554/eLife.01566.002