PCM1 recruits Plk1 to the pericentriolar matrix to promote primary cilia disassembly before mitotic entry.
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.
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.
Gang
G
Wang
Qiang
Q
Chen
Xiaoyan
X
Zhang
Boyan
B
Zhang
Xiaolong
X
Zhuo
Junjun
J
Liu
Qing
Q
Jiang
Chuanmao
C
Zhang
D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism*; D048749:Cytokinesis / Q000235:genetics; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008938:Mitosis; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D000097869:Polo-Like Kinase 1
D001324:Autoantigens; D018797:Cell Cycle Proteins; D000072159:Dynactin Complex; D004398:Dyneins; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases; D008869:Microtubule-Associated Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000097869:Polo-Like Kinase 1; C086074:PCM1 protein, human; C433811:HDAC6 protein, human
PCM1; Plk1; Primary cilium