MOE Key Laboratory of Protein Sciences, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, Shandong Province, China.
PLoS Genet. 2020 Mar 5;16(3):e1008561. doi: 10.1371/journal.pgen.1008561. eCollection 2020 Mar.
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.
纤毛内运输（IFT）是纤毛组装和维持所必需的。虽然 IFT 的破坏可能会引发纤毛解体，但我们在这里表明，IFT 介导的细胞周期蛋白依赖性激酶样激酶的运输可确保纤毛的正确解体。编码细胞周期蛋白依赖性激酶样激酶的纤毛缩短 2 （FLS2）突变导致纤毛吸收的延迟和细胞周期进程的延迟。纤毛解体的刺激诱导 FLS2 的逐渐去磷酸化，伴随着逐渐失活。FLS2 的缺失或其激酶活性诱导动蛋白 13 在纤毛中的早期磷酸化。FLS2 主要定位于细胞体，但在诱导纤毛解体时被转运到纤毛。FLS2 直接与 IFT70 相互作用，丧失这种相互作用抑制其纤毛运输，导致动蛋白 13 磷酸化的失调和纤毛解体的延迟。因此，这项工作表明，IFT 通过将蛋白激酶运输到纤毛来控制适当的纤毛解体，从而在控制适当的纤毛解体中发挥积极作用，以调节微管解聚酶。
