FLA8/KIF3B Phosphorylation Regulates Kinesin-II Interaction with IFT-B to Control IFT Entry and Turnaround
FLA8/KIF3B Phosphorylation Regulates Kinesin-II Interaction with IFT-B to Control IFT Entry and Turnaround
复制标题
FLA8/KIF3B 磷酸化调节驱动蛋白-II 与 IFT-B 的相互作用，以控制 IFT 的进入和周转。
DOI：
10.1016/j.devcel.2014.07.019
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发表时间：
2014-09-08
影响因子：
11.8
通讯作者：
Pan, Junmin
中科院分区：
文献类型：
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作者：
Liang, Yinwen;Pang, Yunong;Pan, Junmin
纤毛的组装和维持依赖于鞭毛内运输（IFT）。激活的IFT运动驱动蛋白-II与包含IFT-A和IFT-B复合物的负载的IFT颗粒一起进入纤毛。在睫状体尖端，驱动蛋白-II变得失活，并且IFT颗粒被释放。此外，在纤毛组装过程中，IFT进入的速率是动态调节的。然而，IFT进入和加载/卸载IFT颗粒的调节机制仍然难以捉摸。我们发现，驱动蛋白-II马达亚基FLA 8，KIF 3B的同源物，在衣原体的钙依赖性激酶的保守的S663磷酸化。这种磷酸化破坏驱动蛋白-II和IFT-B之间的相互作用，使驱动蛋白-II失活并抑制IFT进入，并且也是IFT-B在睫状体尖端卸载所需的。此外，我们的数据表明，IFT进入率是由磷酸化FLA 8的细胞水平的调节控制。因此，FLA 8磷酸化作为分子开关控制IFT进入和周转。
The assembly and maintenance of cilia depends on intraflagellar transport (IFT). Activated IFT motor kinesin-II enters the cilium with loaded IFT particles comprising IFT-A and IFT-B complexes. At the ciliary tip, kinesin-II becomes inactivated, and IFT particles are released. Moreover, the rate of IFT entry is dynamically regulated during cilium assembly. However, the regulatory mechanism of IFT entry and loading/unloading of IFT particles remains elusive. We show that the kinesin-II motor subunit FLA8, a homolog of KIF3B, is phosphorylated on the conserved S663 by a calcium-dependent kinase in Chlamydomonas. This phosphorylation disrupts the interaction between kinesin-II and IFT-B, inactivates kinesin-II and inhibits IFT entry, and is also required for IFT-B unloading at the ciliary tip. Furthermore, our data suggest that the IFT entry rate is controlled by regulation of the cellular level of phosphorylated FLA8. Therefore, FLA8 phosphorylation acts as a molecular switch to control IFT entry and turnaround.