NDEL1 phosphorylation by Aurora-A kinase is essential for centrosomal maturation, separation, and TACC3 recruitment

Daisuke Mori, Yoshihisa Yano, Kazuhito Toyo-Oka, Noriyuki Yoshida, Masami Yamada, Masami Muramatsu, Dongwei Zhang, Hideyuki Saya, Yoko Y. Toyoshima, Kazuhisa Kinoshita, Anthony Wynshaw-Boris, Shinji Hirotsune

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107 Citations (Scopus)

Abstract

NDEL1 is a binding partner of LIS1 that participates in the regulation of cytoplasmic dynein function and microtubule organization during mitotic cell division and neuronal migration. NDEL1 preferentially localizes to the centrosome and is a likely target for cell cycle-activated kinases, including CDK1. In particular, NDEL1 phosphorylation by CDK1 facilitates katanin p60 recruitment to the centrosome and triggers microtubule remodeling. Here, we show that Aurora-A phosphorylates NDEL1 at Ser251 at the beginning of mitotic entry. Interestingly, NDEL1 phosphorylated by Aurora-A was rapidly downregulated thereafter by ubiquitination-mediated protein degradation. In addition, NDEL1 is required for centrosome targeting of TACC3 through the interaction with TACC3. The expression of Aurora-A phosphorylation-mimetic mutants of NDEL1 efficiently rescued the defects of centrosomal maturation and separation which are characteristic of Aurora-A-depleted cells. Our findings suggest that Aurora-A-mediated phosphorylation of NDEL1 is essential for centrosomal separation and centrosomal maturation and for mitotic entry.

Original languageEnglish
Pages (from-to)352-367
Number of pages16
JournalMolecular and cellular biology
Volume27
Issue number1
DOIs
Publication statusPublished - 2007 Jan 1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Mori, D., Yano, Y., Toyo-Oka, K., Yoshida, N., Yamada, M., Muramatsu, M., Zhang, D., Saya, H., Toyoshima, Y. Y., Kinoshita, K., Wynshaw-Boris, A., & Hirotsune, S. (2007). NDEL1 phosphorylation by Aurora-A kinase is essential for centrosomal maturation, separation, and TACC3 recruitment. Molecular and cellular biology, 27(1), 352-367. https://doi.org/10.1128/MCB.00878-06