Coordinating ciliary dynamics and cell proliferation

Abstract

Primary cilia assemble when cells exit the cell cycle and disassemble in proliferating cells to liberate centrioles required for mitotic spindle assembly. Previous studies have shown that Aurora A kinase, a key regulator of cell proliferation, activates histone deacetylase 6 (HDAC6) to deacetylate polymerized tubulin and hence induce the disassembly of cilia. This study reports a key role for Polo-like kinase 1 (PLK1) in the pathway linking ciliary dynamics and cell cycle regulation. It shows that the cell cycle regulator CDK1 phosphorylates the centriolar protein PCM1 before mitotic entry; phosphorylated PCM1 in turn recruits PLK1 to the pericentriolar matrix. PLK1 interacts with and activates HDAC6, thereby inducing cilia disassembly and centriole release. Constitutively active, but not wild-type, PLK1 promotes the disassembly of cilia in the absence of Aurora A activity, which suggests that Aurora A is required to activate PLK1 after recruitment to the pericentriolar matrix.