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

Qin Zhao,Zhengmao Wang,Shufen Li,Shangjin Shao,Junmin Pan,Susan K Dutcher

doi:10.1371/journal.pgen.1008561

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.

Highlights

Cilia are microtubule-based cellular structures that extend from the cell surface
Using the unicellular green alga, Chlamydomonas, we have identified a CDK-like kinase flagellar shortening 2 (FLS2) that when mutated retards cilia resorption, leading to delay of cell cycle progression
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

Summary

Introduction

Cilia are microtubule-based cellular structures that extend from the cell surface. The cellular motility and signaling mediated by cilia plays pivotal roles in physiology and development [1, 2]. Cilia are dynamic structures that undergo assembly and disassembly. They are assembled after cell division and disassembled prior to and/or during mitosis [4,5,6,7]. They are subjected to disassembly during cell differentiation and in response to cellular stress [8,9,10]. Deciliation has been reported as a predominant mode of ciliary disassembly during cell cycle progression in mammalian cells [15]. Several studies suggest that ciliary disassembly is related to tumorigenesis because primary cilia are disassembled in a variety of cancer types [22]

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