Identification of a novel Wnt5a-CK1ɛ-Dvl2-Plk1-mediated primary cilia disassembly pathway

EMBO J. 2012 May 18;31(14):3104-17. doi: 10.1038/emboj.2012.144.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Aurora Kinase A
  • Aurora Kinases
  • Casein Kinase Iepsilon / genetics
  • Casein Kinase Iepsilon / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cilia / genetics
  • Cilia / metabolism
  • Dishevelled Proteins
  • HeLa Cells
  • Humans
  • L Cells
  • Mice
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • Wnt-5a Protein

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • DVL2 protein, human
  • Dishevelled Proteins
  • Dvl2 protein, mouse
  • Multienzyme Complexes
  • NEDD9 protein, human
  • NEDD9 protein, mouse
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • WNT5A protein, human
  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt5a protein, mouse
  • Aurka protein, mouse
  • Aurora Kinase A
  • Aurora Kinases
  • Casein Kinase Iepsilon
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1