title: Identification of a novel Wnt5a-CK1ɛ-Dvl2-Plk1-mediated primary cilia disassembly pathway.
abstract: Non-motile primary cilium is an antenna-like structure whose defect is associated with a wide range of pathologies, including developmental disorders and cancer. Although mechanisms regulating cilia assembly have been extensively studied, how cilia disassembly is regulated remains poorly understood. Here, we report unexpected roles of Dishevelled 2 (Dvl2) and interphase polo-like kinase 1 (Plk1) in primary cilia disassembly. We demonstrated that Dvl2 is phosphorylated at S143 and T224 in a manner that requires both non-canonical Wnt5a ligand and casein kinase 1 epsilon (CK1ɛ), and that this event is critical to interact with Plk1 in early stages of the cell cycle. The resulting Dvl2-Plk1 complex mediated Wnt5a-CK1ɛ-Dvl2-dependent primary cilia disassembly by stabilizing the HEF1 scaffold and activating its associated Aurora-A (AurA), a kinase crucially required for primary cilia disassembly. Thus, via the formation of the Dvl2-Plk1 complex, Plk1 plays an unanticipated role in primary cilia disassembly by linking Wnt5a-induced biochemical steps to HEF1/AurA-dependent cilia disassembly. This study may provide new insights into the mechanism underlying ciliary disassembly processes and various cilia-related disorders.
authors.affiliation: Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Johmura
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Yu
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Park
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Jeong K
authors.initials: JK
authors.lastname: Bang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Veenstra
authors.forename: Bo
authors.initials: B
authors.lastname: Yeon Kim
authors.forename: Kyung S
authors.initials: KS
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D064096:Aurora Kinase A; D064127:Aurora Kinases; D048149:Casein Kinase 1 epsilon / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002923:Cilia / Q000235:genetics / Q000378:metabolism; D000072261:Dishevelled Proteins; D006367:HeLa Cells; D006801:Humans; D007739:L Cells; D051379:Mice; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein; D000097869:Polo-Like Kinase 1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D064096:Aurora Kinase A; D064127:Aurora Kinases; D048149:Casein Kinase 1 epsilon; D018797:Cell Cycle Proteins; D000072261:Dishevelled Proteins; D009097:Multienzyme Complexes; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D000097869:Polo-Like Kinase 1; C000606581:DVL2 protein, human; C000606582:Dvl2 protein, mouse; C099942:NEDD9 protein, human; C505592:NEDD9 protein, mouse; C085389:WNT5A protein, human; C438615:Wnt5a protein, mouse; C576918:Aurka protein, mouse