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LATS2-Ajuba complex regulates gamma-tubulin recruitment to centrosomes and spindle organization during mitosis

Yoshinori Abe1, Miho Ohsugi, Keiko Haraguchi

  • 1Division of Oncology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Tokyo 108-8639, Japan.

FEBS Letters
|January 18, 2006
PubMed

Insights

The large tumor suppressor kinase 2 (LATS2) and Ajuba complex regulate cell division by recruiting gamma-tubulin to centrosomes. This interaction is crucial for proper spindle formation during mitosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Large tumor suppressor kinase 2 (LATS2) is a human homolog of Drosophila tumor suppressor lats/warts.
  • LATS2 is a mitotic kinase with largely unknown physiological functions.
  • The role of LATS2 in cell cycle regulation and its interaction partners require further elucidation.

Purpose of the Study:

  • To identify binding partners of LATS2 using yeast two-hybrid screening.
  • To investigate the role of LATS2 and its binding partner in mitotic regulation.
  • To elucidate the function of the LATS2-Ajuba complex in centrosome organization and spindle formation.

Main Methods:

  • Yeast two-hybrid screening to identify LATS2 binding partners.
  • Immunofluorescence microscopy to determine subcellular localization of LATS2 and Ajuba.
  • Western blotting to assess mitotic phosphorylation of Ajuba.
  • RNA interference (RNAi) to deplete LATS2 or Ajuba expression.
  • Analysis of centrosomal gamma-tubulin accumulation and spindle formation.

Main Results:

  • Ajuba, a LIM protein, was identified as a binding partner of LATS2.
  • LATS2 localizes to centrosomes throughout the cell cycle and interacts with Ajuba during mitosis.
  • LATS2 contributes to the mitotic phosphorylation of Ajuba.
  • Depletion of LATS2 or Ajuba disrupted centrosomal accumulation of gamma-tubulin.
  • Impaired spindle formation was observed at the onset of mitosis in LATS2- or Ajuba-depleted cells.

Conclusions:

  • The LATS2-Ajuba complex plays a critical role in regulating the organization of the spindle apparatus.
  • This regulation occurs through the recruitment of gamma-tubulin to the centrosome.
  • LATS2 and Ajuba are essential for proper centrosome function and spindle assembly during mitosis.

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