Journal of Cell Science PCM1 recruits Plk1 to the pericentriolar matrix to promote primary cilia disassembly before mitotic entry Gang Wang 1, *, Qiang Chen 1, *, Xiaoyan Zhang 1 , Boyan Zhang 1 , Xiaolong Zhuo 1 , Junjun Liu 2 , Qing Jiang 1 and Chuanmao Zhang 1,` 1 MOE Key Laboratory of Cell Proliferation and Differentiation and State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China 2 Department of Biological Sciences, California State Polytechnic University, Pomona, CA 91768, USA *These authors contributed equally to this work ` Author for correspondence (zhangcm@pku.edu.cn) Accepted 11 December 2012 Journal of Cell Science 126, 1355–1365 ß 2013. Published by The Company of Biologists Ltd doi: 10.1242/jcs.114918 Summary Primary cilia, which emanate from the cell surface, exhibit assembly and disassembly dynamics along the progression of the cell cycle. However, the mechanism that links ciliary dynamics and cell cycle regulation remains elusive. In the present study, we report that Polo- like kinase 1 (Plk1), one of the key cell cycle regulators, which regulate centrosome maturation, bipolar spindle assembly and cytokinesis, acts as a pivotal player that connects ciliary dynamics and cell cycle regulation. We found that the kinase activity of centrosome enriched Plk1 is required for primary cilia disassembly before mitotic entry, wherein Plk1 interacts with and activates histone deacetylase 6 (HDAC6) to promote ciliary deacetylation and resorption. Furthermore, we showed that pericentriolar material 1 (PCM1) acts upstream of Plk1 and recruits the kinase to pericentriolar matrix (PCM) in a dynein-dynactin complex-dependent manner. This process coincides with the primary cilia disassembly dynamics at the onset of mitosis, as depletion of PCM1 by shRNA dramatically disrupted the pericentriolar accumulation of Plk1. Notably, the interaction between PCM1 and Plk1 is phosphorylation dependent, and CDK1 functions as the priming kinase to facilitate the interaction. Our data suggest a mechanism whereby the recruitment of Plk1 to pericentriolar matrix by PCM1 plays a pivotal role in the regulation of primary cilia disassembly before mitotic entry. Thus, the regulation of ciliary dynamics and cell proliferation share some common regulators. Key words: PCM1, Plk1, Primary cilium Introduction Primary cilium is an important cell organelle that assembles based on basal body and projects from cell surface, which plays critical roles in sensation and cellular signal transduction owning to the enrichment of receptors and channels on ciliary membrane (Berbari et al., 2009; Singla and Reiter, 2006). The defects of primary cilia function lead to numerous cilium-related human diseases, such as Bardet-Biedl Syndrome (BBS), retinal degeneration, polycystic kidney disease and other disorders (Ishikawa and Marshall, 2011). Primary cilia assemble when cells exit from cell cycle and enter quiescence, while the cilia of proliferating cells often exhibit dynamic probably due to the fact that cilia disassembly liberates centrioles to undergo duplication and separation for bipolar spindle assembly, although centriole duplication can also take place while the mother centriole still acts as the ciliary basal body (Fonte et al., 1971; Quarmby and Parker, 2005; Rieder, 1979; Seeley and Nachury, 2010; Uetake et al., 2007). Ciliogenesis is strikingly controlled, and numerous evidences have shown that intraflagellar transport (IFT), membrane trafficking and cilia associated proteins, such as BBSome, are involved (Follit et al., 2006; Ishikawa and Marshall, 2011; Jin et al., 2010; Nachury et al., 2007; Pedersen and Rosenbaum, 2008; Qin et al., 2005). Over the past decades, evidences have shown that the cilia assembly and disassembly dynamics accompany with the cell cycle. However, the detailed mechanisms underlying the relationship between cell proliferation and ciliary dynamics remain elusive, though both Pitchfork and HEF1 were revealed recently to be responsible for the cilia disassembly by regulating Aurora A activity, which subsequently phosphorylates and activates HDAC6 to regulate the primary cilia resorption (Kinzel et al., 2010; Pugacheva et al., 2007). Centrosome maturation is a crucial step for the bipolar mitotic spindle assembly and this process has been characterized in principal by the features of the recruitment and re-organization of additional pericentriolar material, the phosphorylation of centrosomal proteins and the dramatic increase of the microtubule nucleation and anchoring capacity of the centrosome (Bornens, 2002; Schatten, 2008). A number of mitotic protein kinases, including Plk1, Aurora A and CDK1, are crucial for the maturation of centrosome by phosphorylating the centrosomal proteins. In addition, in the recruitment of additional pericentriolar materials, Nedd1 is required for maturation and microtubule nucleation of the centrosome by targeting c-TuRC to centrosome at the G2/M phase transition, and this process needs Nedd1 to be sequentially phosphorylated by CDK1 and Plk1 (Haren et al., 2006; Lu ¨ders et al., 2006; Schatten, 2008; Zhang et al., 2009). Also, activated Plk1 could phosphorylate Ninein-like protein (Nlp) to promote its displacement from maturing centrosome, and the displacement is important for mitotic Research Article 1355