Dishevelled, a Wnt signalling component, is involved in mitotic progression in cooperation with Plk1

EMBO J. 2010 Oct 20;29(20):3470-83. doi: 10.1038/emboj.2010.221. Epub 2010 Sep 7.

Abstract

Wnt signalling is known to promote G1/S progression through the stimulation of gene expression, but whether this signalling regulates mitotic progression is not clear. Here, the function of dishevelled 2 (Dvl2), which transmits the Wnt signal, in mitosis was examined. Dvl2 localized to the spindles and spindle poles during mitosis. When cells were treated with nocodazole, Dvl2 was observed at the kinetochores (KTs). Dvl2 bound to and was phosphorylated at Thr206 by a mitotic kinase, Polo-like kinase 1 (Plk1), and this phosphorylation was required for spindle orientation and stable microtubule (MT)-KT attachment. Dvl2 was also found to be involved in the activation of a spindle assembly checkpoint (SAC) kinase, Mps1, and the recruitment of other SAC components, Bub1 and BubR1, to the KTs. However, the phosphorylation of Dvl2 by Plk1 was dispensable for SAC. Furthermore, Wnt receptors were involved in spindle orientation, but not in MT-KT attachment or SAC. These results suggested that Dvl2 is involved in mitotic progression by regulating the dynamics of MT plus-ends and the SAC in Plk1-dependent and -independent manners.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Autoantigens / genetics
  • Autoantigens / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Dishevelled Proteins
  • Frizzled Receptors / genetics
  • Frizzled Receptors / metabolism
  • Humans
  • Kinetochores / metabolism
  • Low Density Lipoprotein Receptor-Related Protein-6
  • Mitosis / physiology*
  • Nocodazole / metabolism
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, LDL / genetics
  • Receptors, LDL / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / physiology*
  • Spindle Apparatus / metabolism
  • Tubulin Modulators / metabolism
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Autoantigens
  • Cell Cycle Proteins
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone
  • DVL2 protein, human
  • Dishevelled Proteins
  • FZD2 protein, human
  • Frizzled Receptors
  • LRP6 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-6
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Receptors, G-Protein-Coupled
  • Receptors, LDL
  • Recombinant Fusion Proteins
  • Tubulin Modulators
  • Wnt Proteins
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1
  • Nocodazole