IFT54 directly interacts with kinesin‐II and IFT dynein to regulate anterograde intraflagellar transport
IFT54 directly interacts with kinesin‐II and IFT dynein to regulate anterograde intraflagellar transport
复制标题
DOI：
10.15252/embj.2020105781
复制
发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Xin Zhu;Jieling Wang;Shufen Li;K. Lechtreck;Junmin Pan
中科院分区：
文献类型：
--
作者：
Xin Zhu;Jieling Wang;Shufen Li;K. Lechtreck;Junmin Pan
鞭毛内运输（IFT）机制由顺行运动驱动蛋白- II、逆行运动IFT动力蛋白以及IFT - A和- B复合物组成。然而，在IFT过程中，IFT马达和IFT复合物之间的相互作用仍然是难以捉摸的。在这里，我们发现IFT - B蛋白IFT54与kinesin - II和IFT动力蛋白相互作用，并调节顺行IFT。衣藻IFT54残基342 ~ 356的缺失导致IFT的顺行交通减少，以及纤毛近端IFT马达和复合物的积累。IFT54直接与kinesin‐II相互作用，这种相互作用在体内和体外的IFT54Δ342-356突变体中都得到了加强。IFT54残基261-275的缺失减少了IFT动力蛋白的纤毛进入和顺行运输，并在纤毛尖端附近积累了IFT复合物。IFT54直接与IFT动力蛋白亚基D1bLIC相互作用，残基261-275的缺失减少了这种相互作用。在哺乳动物细胞中也观察到IFT54和IFT马达之间的相互作用。我们的数据表明，在顺行IFT期间，IFT54在结合IFT马达方面发挥了核心作用。
The intraflagellar transport (IFT) machinery consists of the anterograde motor kinesin‐II, the retrograde motor IFT dynein, and the IFT‐A and ‐B complexes. However, the interaction among IFT motors and IFT complexes during IFT remains elusive. Here, we show that the IFT‐B protein IFT54 interacts with both kinesin‐II and IFT dynein and regulates anterograde IFT. Deletion of residues 342–356 of Chlamydomonas IFT54 resulted in diminished anterograde traffic of IFT and accumulation of IFT motors and complexes in the proximal region of cilia. IFT54 directly interacted with kinesin‐II and this interaction was strengthened for the IFT54Δ342–356 mutant in vitro and in vivo. The deletion of residues 261–275 of IFT54 reduced ciliary entry and anterograde traffic of IFT dynein with accumulation of IFT complexes near the ciliary tip. IFT54 directly interacted with IFT dynein subunit D1bLIC, and deletion of residues 261–275 reduced this interaction. The interactions between IFT54 and the IFT motors were also observed in mammalian cells. Our data indicate a central role for IFT54 in binding the IFT motors during anterograde IFT.