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bioRxiv · 10.1101/871376

FLS2 is a CDK-like kinase that directly binds IFT70 and is required for proper ciliary disassembly in Chlamydomonas

Zhao, Q.·Li, S.·Shao, S.·Wang, Z.·Pan, J.
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Abstract

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 SummaryCilia 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.

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Zhao, Q., Li, S., Shao, S., Wang, Z., Pan, J.. 2019-12-10. FLS2 is a CDK-like kinase that directly binds IFT70 and is required for proper ciliary disassembly in Chlamydomonas. https://doi.org/10.1101/871376

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