Characterization of tetratricopeptide repeat-containing proteins critical for cilia formation and function.
Characterization of tetratricopeptide repeat-containing proteins critical for cilia formation and function.
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对纤毛形成和功能至关重要的四肽重复蛋白的表征
DOI：
10.1371/journal.pone.0124378
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Yan X
中科院分区：
文献类型：
--
作者：
Xu Y;Cao J;Huang S;Feng D;Zhang W;Zhu X;Yan X
纤毛的形成和功能需要一套特殊的运输机制，称为鞭毛内运输（IFT），主要由蛋白质复合物IFT-A，IFT-B，BBSome和微管依赖性分子马达组成。含三肽重复序列（TTC）蛋白广泛参与蛋白质复合物的形成。其中9个已知作为IFT或BBSome复合物的组分。然而，有多少TTC蛋白与纤毛相关，以及它们如何发挥作用，目前尚不清楚。在这里，我们发现，20 TTC基因上调至少2倍，在培养的小鼠气管上皮细胞（MTEC）分化成多纤毛细胞。我们在斑马鱼中的系统筛选鉴定了四个新的TTC基因，ttc 4，-9c，-36和-39c，它们对纤毛的形成和运动至关重要。因此，他们的斑马鱼变形显示出典型的纤毛病变相关的表型，包括弯曲的身体，异常耳石，脑积水，和缺陷的左右图案。已知的纤毛相关基因ttc 4和ttc 25的突变体也显示了前肾囊肿的形成。免疫沉淀表明TTC 4、-9c、-25、-36和-39c与IFT-A、IFT-B或BBSome的组分或整个复合物相关，这意味着它们参与IFT或IFT相关活性。我们的研究结果为TTC蛋白和纤毛之间的关系提供了一个全局视图。
Cilia formation and function require a special set of trafficking machinery termed intraflagellar transport (IFT), consisting mainly of protein complexes IFT-A, IFT-B, BBSome, and microtubule-dependent molecular motors. Tetratricopeptide repeat-containing (TTC) proteins are widely involved in protein complex formation. Nine of them are known to serve as components of the IFT or BBSome complexes. How many TTC proteins are cilia-related and how they function, however, remain unclear. Here we show that twenty TTC genes were upregulated by at least 2-fold during the differentiation of cultured mouse tracheal epithelial cells (MTECs) into multiciliated cells. Our systematic screen in zebrafish identified four novel TTC genes, ttc4, -9c, -36, and -39c, that are critical for cilia formation and motility. Accordingly, their zebrafish morphants displayed typical ciliopathy-related phenotypes, including curved body, abnormal otolith, hydrocephalus, and defective left-right patterning. The morphants of ttc4 and ttc25, a known cilia-related gene, additionally showed pronephric cyst formation. Immunoprecipitation indicated associations of TTC4, -9c, -25, -36, and -39c with components or entire complexes of IFT-A, IFT-B, or BBSome, implying their participations in IFT or IFT-related activities. Our results provide a global view for the relationship between TTC proteins and cilia.
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影响因子：
64.8
作者：
Ou, GS;Blacque, OE;Scholey, JM
通讯作者：
Scholey, JM
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.6
作者：
Franklin JB;Ullu E
通讯作者：
Ullu E
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。
影响因子：
7.7
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
通讯作者：
Marshall WF
影响因子：
4
作者：
Hao, Limin;Scholey, Jonathan M.
通讯作者：
Scholey, Jonathan M.