Li Yuanyuan, Zhao Lu, Yuan Shiaulou, Zhang Jiefang, Sun Zhaoxia
Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA.
Development. 2017 Dec 15;144(24):4684-4693. doi: 10.1242/dev.152314. Epub 2017 Nov 7.
Pontin (Ruvbl1) and Reptin (Ruvbl2) are closely related AAA ATPases. They are components of the Ruvbl1-Ruvbl2-Tah1-Pih1 (R2TP) complexes that function as co-chaperones for the assembly of multiple macromolecular protein complexes. Here, we show that Pontin is essential for cilia motility in both zebrafish and mouse and that Pontin and Reptin function cooperatively in this process. Zebrafish mutants display phenotypes tightly associated with cilia defects, and cilia motility is lost in a number of ciliated tissues along with a reduction in the number of outer and inner dynein arms. Pontin protein is enriched in cytosolic puncta in ciliated cells in zebrafish embryos. In mouse testis, Pontin is essential for the stabilization of axonemal dynein intermediate chain 1 (DNAI1) and DNAI2, the first appreciated step in axonemal dynein arm assembly. Strikingly, multiple dynein arm assembly factors show structural similarities to either Tah1 or Pih1, the other two components of the R2TP complex. Based on these results, we propose that Pontin and Reptin function to facilitate dynein arm assembly in cytosolic foci enriched with R2TP-like complexes.
庞廷（Ruvbl1）和雷ptin（Ruvbl2）是密切相关的AAA型ATP酶。它们是Ruvbl1-Ruvbl2-Tah1-Pih1（R2TP）复合物的组成部分，该复合物作为多种大分子蛋白质复合物组装的共伴侣发挥作用。在这里，我们表明庞廷对斑马鱼和小鼠的纤毛运动至关重要，并且庞廷和雷ptin在这个过程中协同发挥作用。斑马鱼突变体表现出与纤毛缺陷紧密相关的表型，并且在许多纤毛组织中纤毛运动丧失，同时外动力蛋白臂和内动力蛋白臂的数量减少。庞廷蛋白在斑马鱼胚胎的纤毛细胞的胞质斑点中富集。在小鼠睾丸中，庞廷对于轴丝动力蛋白中间链1（DNAI1）和DNAI2的稳定至关重要，这是轴丝动力蛋白臂组装中首先被认识到的步骤。引人注目的是，多种动力蛋白臂组装因子与R2TP复合物的另外两个组分Tah1或Pih1具有结构相似性。基于这些结果，我们提出庞廷和雷ptin的功能是促进富含R2TP样复合物的胞质焦点中的动力蛋白臂组装。
