β-catenin is a Nek2 substrate involved in centrosome separation

Shirin Bahmanyar, Daniel D. Kaplan, Jennifer G. DeLuca, Thomas H. Giddings, Eileen T. O'Toole, Mark Winey, Edward D. Salmon, Patrick J. Casey, W. James Nelson, Angela I.M. Barth

Research output: Contribution to journalArticle

154 Scopus citations

Abstract

β-Catenin plays important roles in cell adhesion and gene transcription, and has been shown recently to be essential for the establishment of a bipolar mitotic spindle. Here we show that β-catenin is a component of interphase centrosomes and that stabilization of β-catenin, mimicking mutations found in cancers, induces centrosome splitting. Centrosomes are held together by a dynamic linker regulated by Nek2 kinase and its substrates C-Nap1 (centrosomal Nek2-associated protein 1) and Rootletin. We show that β-catenin binds to and is phosphorylated by Nek2, and is in a complex with Rootletin. In interphase, β-catenin colocalizes with Rootletin between C-Nap1 puncta at the proximal end of centrioles, and this localization is dependent on C-Nap1 and Rootletin. In mitosis, when Nek2 activity increases, β-catenin localizes to centrosomes at spindle poles independent of Rootletin. Increased Nek2 activity disrupts the interaction of Rootletin with centrosomes and results in binding of β-catenin to Rootletin-independent sites on centrosomes, an event that is required for centrosome separation. These results identify β-catenin as a component of the intercentrosomal linker and define a new function for β-catenin as a key regulator of mitotic centrosome separation.

Original languageEnglish (US)
Pages (from-to)91-105
Number of pages15
JournalGenes and Development
Volume22
Issue number1
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

Keywords

  • β-Catenin
  • C-Nap1
  • Centrosome
  • Mitosis
  • Nek2
  • Rootletin

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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  • Cite this

    Bahmanyar, S., Kaplan, D. D., DeLuca, J. G., Giddings, T. H., O'Toole, E. T., Winey, M., Salmon, E. D., Casey, P. J., Nelson, W. J., & Barth, A. I. M. (2008). β-catenin is a Nek2 substrate involved in centrosome separation. Genes and Development, 22(1), 91-105. https://doi.org/10.1101/gad.1596308