MST2- and Furry-Mediated Activation of NDR1 Kinase Is Critical for Precise Alignment of Mitotic Chromosomes

Shuhei Chiba, Masanori Ikeda, Kokichi Katsunuma, Kazumasa Ohashi, Kensaku Mizuno

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

The precise alignment of chromosomes on the metaphase plate prior to the onset of anaphase is essential for ensuring equal segregation of sister chromatids into two daughter cells, and defects in this process potentially cause chromosome instability and tumor progression [1-3]. NDR1 is an evolutionarily conserved serine/threonine kinase whose activity is regulated by MST kinases, Furry (Fry), and MOB [4]. Although the NDR1 signaling pathway is implicated in cell division and morphogenesis in yeast and invertebrates [4-16], the mechanisms of NDR1 activation and the functional significance of the NDR1 pathway in mammalian cells are largely unknown. Here, we show that NDR1 is required for accurate chromosome alignment at metaphase in HeLa cells; depletion of NDR1, Fry, or MST2 caused mitotic chromosome misalignment. Chromosome misalignment in MST2-depleted cells was corrected by expression of active NDR1. The kinase activity of NDR1 increased in early mitotic phase and was dependent on Fry and MST2. We also provide evidence that Fry binds to microtubules, localizes on the spindle, acts as a scaffold that binds to both NDR1 and MOB2, and synergistically activates NDR1 with MOB2. Our findings suggest that MST2-, Fry-, and MOB2-mediated activation of NDR1 is crucial for the fidelity of mitotic chromosome alignment in mammalian cells.

Original languageEnglish
Pages (from-to)675-681
Number of pages7
JournalCurrent Biology
Volume19
Issue number8
DOIs
Publication statusPublished - 2009 Apr 28

Keywords

  • CELLBIO

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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