Ciliary Length Sensing Regulates IFT Entry via Changes in FLA8/KIF3B Phosphorylation to Control Ciliary Assembly
Ciliary Length Sensing Regulates IFT Entry via Changes in FLA8/KIF3B Phosphorylation to Control Ciliary Assembly
复制标题
纤毛长度传感通过 FLA8/KIF3B 磷酸化的变化来调节 IFT 进入以控制纤毛组装
DOI：
10.1016/j.cub.2018.05.069
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发表时间：
2018-08-06
期刊：
影响因子：
9.2
通讯作者：
Pan, Junmin
中科院分区：
文献类型：
--
作者：
Liang, Yinwen;Zhu, Xin;Pan, Junmin
纤毛的长度受到严格的控制[1]。先前的数据表明，细胞具有控制纤毛长度的传感系统[2-5]。然而，该机制的细节目前尚不清楚[6，7]。这种系统需要一种对纤毛长度做出响应的机制，因此，该响应系统的破坏应该改变纤毛长度[1]。由鞭毛内转运（IFT）介导的纤毛组装速率随着纤毛的伸长而逐渐降低，最终被恒定的解体速率所平衡，此时纤毛的伸长停止[8，9]。由于IFT进入纤毛的速率也随着纤毛的伸长而降低[10]，因此IFT进入的调节可以提供长度控制的机制。以前，我们发现，在衣原体中，顺行驱动蛋白-II IFT马达的FLA 8/KIF 3B亚基的磷酸化阻断IFT进入和鞭毛组装[11]。在这里，我们显示在衣原体，细胞信号在响应鞭毛长度的改变调节FLA 8/KIF 3B，这限制IFT进入磷酸化，因此，鞭毛组装控制鞭毛长度。磷酸化FLA 8（pFLA 8）的细胞水平与鞭毛长度紧密相关：FLA 8磷酸化在具有短鞭毛的细胞中减少，而在具有长鞭毛的细胞中升高。磷酸酶CrPP 1和CrPP 6的消耗增加了细胞pFLA 8的水平，导致由于IFT进入减少而导致的短鞭毛。结果表明，纤毛长度控制是通过细胞传感系统，控制通过磷酸化的顺行IFT马达IFT进入。
The length of cilia is robustly regulated [1]. Previous data suggest that cells possess a sensing system to control ciliary length [2-5]. However, the details of the mechanism are currently not known [6, 7]. Such a system requires a mechanism that responds to ciliary length, and consequently, disruption of that response system should alter ciliary length [1]. The assembly rate of cilium mediated by intraflagellar transport (IFT) gradually decreases as the cilium elongates and eventually is balanced by the constant rate of disassembly, at which point cilium elongation stops [8, 9]. Because the rate of IFT entry into the cilium also decreases as the cilium elongates [10], regulation of IFT entry could provide the mechanism for length control. Previously, we showed that phosphorylation of the FLA8/KIF3B subunit of the anterograde kinesin-II IFT motor blocks IFT entry and flagellar assembly in Chlamydomonas [11]. Here, we show in Chlamydomonas that cellular signaling in response to alteration of flagellar length regulates phosphorylation of FLA8/KIF3B, which restricts IFT entry and, thus, flagellar assembly to control flagellar length. Cellular levels of phosphorylated FLA8 (pFLA8) are tightly linked to flagellar length: FLA8 phosphorylation is reduced in cells with short flagella and elevated in cells with long flagella. Depletion of the phosphatases CrPP1 and CrPP6 increases the level of cellular pFLA8, leading to short flagella due to decreased IFT entry. The results demonstrate that ciliary length control is achieved by a cellular sensing system that controls IFT entry through phosphorylation of the anterograde IFT motor.