β-Catenin is a Nek2 substrate involved in centrosome separation

  1. Shirin Bahmanyar1,6,
  2. Daniel D. Kaplan2,3,6,
  3. Jennifer G. DeLuca4,7,
  4. Thomas H. Giddings, Jr.5,
  5. Eileen T. O’Toole5,
  6. Mark Winey5,
  7. Edward D. Salmon4,
  8. Patrick J. Casey2,
  9. W. James Nelson1, and
  10. Angela I.M. Barth1,8
  1. 1 Departments of Biological Sciences, and Molecular and Cellular Physiology, Stanford University, Stanford, California 94305, USA;
  2. 2 Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA;
  3. 3 Department of Developmental Biology, and Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California 94305, USA;
  4. 4 Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA;
  5. 5 Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA

  1. ↵6 These authors contributed equally to this work.

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.

Keywords

Footnotes

  • ↵7 Present address: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA.

  • ↵8 Corresponding author.

    ↵8 E-MAIL angelab{at}stanford.edu; FAX (650) 724-4927.

  • Supplemental material is available at http://www.genesdev.org.

  • Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.1596308

    • Received July 23, 2007.
    • Accepted November 2, 2007.
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  1. Published in Advance December 17, 2007, doi: 10.1101/gad.1596308 Genes & Dev. 22: 91-105 Copyright © 2008, Cold Spring Harbor Laboratory Press

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