FLS2 is a CDK-like kinase that directly binds IFT70 and is required for proper ciliary disassembly in Chlamydomonas
FLS2 is a CDK-like kinase that directly binds IFT70 and is required for proper ciliary disassembly in Chlamydomonas
复制标题
FLS2 是一种 CDK 样激酶，可直接结合 IFT70，是衣藻中纤毛正确分解所必需的
DOI：
10.1371/journal.pgen.1008561
复制
发表时间：
2020-03-01
期刊：
影响因子：
4.5
通讯作者：
Pan，Junmin
中科院分区：
文献类型：
--
作者：
Zhao，Qin;Li，Shufen;Pan，Junmin
鞭毛内转运（IFT）是纤毛组装和维持所必需的。虽然IFT的破坏可能会触发纤毛解体，我们在这里表明，IFT介导的CDK样激酶的运输，确保适当的纤毛解体。编码CDK样激酶的鞭毛缩短2（FLS2）突变导致纤毛吸收延迟和细胞周期进展延迟。刺激纤毛解体诱导FLS2的逐渐去磷酸化，伴随着逐渐失活。FLS2或其激酶活性的丧失诱导纤毛中驱动蛋白13磷酸化的早期发作。FLS2主要定位于细胞体中，然而，其在诱导纤毛解体后被转运至纤毛。FLS2直接与IFFT 70相互作用，这种相互作用的丧失抑制其纤毛转运，导致驱动蛋白13磷酸化的失调和纤毛解体的延迟。因此，这项工作表明，IFT在控制适当的纤毛解体中发挥积极作用，通过转运蛋白激酶到纤毛调节微管解聚。纤毛或真核生物鞭毛是细胞表面的突起，在细胞运动以及传感功能。它们是经历组装和拆卸的动态结构。纤毛在细胞周期进程中被再吸收。纤毛再吸收的失调可能导致细胞周期进程的延迟，这是异常细胞分化甚至癌症的基础。纤毛吸收需要由驱动蛋白13介导的轴丝微管的去聚合。使用单细胞绿色真菌，衣原体，我们已经确定了一个CDK样激酶FLS2，当突变延迟纤毛吸收，导致细胞周期进程的延迟。FLS2是一种细胞体蛋白，在诱导纤毛吸收后通过鞭毛内转运转运至纤毛。FLS2直接与IFFT 70相互作用，这种相互作用的丧失抑制FLS2向纤毛的转运，并且不能调节纤毛中驱动蛋白13的适当磷酸化。
Intraflagellar transport (IFT) is required for ciliary assembly and maintenance. While disruption of IFT may trigger ciliary disassembly, we show here that IFT mediated transport of a CDK-like kinase ensures proper ciliary disassembly. Mutations in flagellar shortening 2 (FLS2), encoding a CDK-like kinase, lead to retardation of cilia resorption and delay of cell cycle progression. Stimulation for ciliary disassembly induces gradual dephosphorylation of FLS2 accompanied with gradual inactivation. Loss of FLS2 or its kinase activity induces early onset of kinesin13 phosphorylation in cilia. FLS2 is predominantly localized in the cell body, however, it is transported to cilia upon induction of ciliary disassembly. FLS2 directly interacts with IFT70 and loss of this interaction inhibits its ciliary transport, leading to dysregulation of kinesin13 phosphorylation and retardation of ciliary disassembly. Thus, this work demonstrates that IFT plays active roles in controlling proper ciliary disassembly by transporting a protein kinase to cilia to regulate a microtubule depolymerizer. Author Summary Cilia or eukaryotic flagella are cellular surface protrusions that function in cell motility as well as sensing. They are dynamic structures that undergo assembly and disassembly. Cilia are resorbed during cell cycle progression. Dysregulation of cilia resorption may cause delay of cell cycle progression, which underlies aberrant cell differentiation and even cancer. Ciliary resorption requires depolmerization of axonemal microtubules that is mediated by kinesin13. Using the unicellular green alga, Chlamydomonas, we have identified a CDK-like kinase FLS2 that when mutated retards cilia resorption, leading to delay of cell cycle progression. FLS2, a cell body protein, is transported to cilia via intraflagellar transport upon induction of cilia resorption. FLS2 directly interacts with IFT70 and loss of this interaction inhibits transport of FLS2 to cilia and fails to regulate proper phosphorylation of kinesin13 in cilia.