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Microtubule stabilization triggers the plus-end accumulation of Kif18A/kinesin-8

Natsuko Masuda1, Tetsuhiro Shimodaira, Shu-Jen Shiu

  • 1Division of Oncology, Department of Cancer Biology, Institute of Medical Science, The University of Tokyo, Japan.

Cell Structure and Function
|November 23, 2011
PubMed

Insights

Kinesin-8 (Kif18A) accumulates at microtubule plus-ends, crucial for chromosome alignment. This accumulation depends on microtubule dynamics, not just kinetochore attachment, revealing a mutual regulation mechanism.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biophysics

Background:

  • Precise control of spindle microtubule (MT) dynamics is vital for accurate chromosome segregation during cell division.
  • Kif18A, a kinesin-8 motor protein, regulates kinetochore MT dynamics and accumulates at MT plus-ends during metaphase, but the mechanism remains unclear.

Purpose of the Study:

  • To investigate the factors governing the time-dependent and kinetochore MT-specific plus-end accumulation of Kif18A.
  • To elucidate the relationship between Kif18A accumulation and its role in MT length control.

Main Methods:

  • Utilized Eg5 and Aurora B inhibitors to manipulate spindle assembly and MT dynamics in cultured cells.
  • Observed Kif18A localization and MT length in response to drug treatments and Kif18A depletion.
  • Assessed MT plus-end association and kinetochore MT stability.

Main Results:

  • Kif18A plus-end accumulation requires specific MT dynamics, as Eg5 inhibition (monopolar spindles) prevented accumulation despite MT-kinetochore association.
  • Taxol treatment induced rapid Kif18A plus-end accumulation independent of kinetochore attachment.
  • Aurora B inhibition, which stabilizes MT plus-ends, promoted Kif18A accumulation.
  • Kif18A depletion led to MT elongation upon taxol treatment, highlighting Kif18A's role in MT length regulation via plus-end accumulation.

Conclusions:

  • Kif18A accumulation at MT plus-ends is regulated by MT dynamics and stabilization, not solely by kinetochore attachment.
  • A mutual regulatory loop exists between kinetochore MT plus-end dynamics and Kif18A accumulation.
  • This interplay is critical for ordered MT dynamics during chromosome congression and oscillation in mitosis.

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