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Plk1 and Aurora A regulate the depolymerase activity and the cellular localization of Kif2a
Chang-Young Jang1, Judith A Coppinger, Akiko Seki
1Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
Journal of Cell Science
|April 9, 2009
Summary
Polo-like kinase 1 (Plk1) and Aurora A antagonistically regulate Kif2a, a key protein in cell division. This control fine-tunes microtubule stability, ensuring proper spindle assembly and chromosome segregation.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Kif2a is a microtubule depolymerase crucial for spindle assembly, chromosome congression, and segregation during mitosis.
- Understanding the regulation of Kif2a is vital for comprehending cell division fidelity.
Purpose of the Study:
- To identify regulators of Kif2a activity.
- To elucidate the mechanisms by which Plk1 and Aurora A modulate Kif2a function.
- To investigate the impact of this regulation on spindle dynamics and cell division.
Main Methods:
- Proteomic analysis to identify Kif2a interacting proteins.
- In vitro kinase assays to assess phosphorylation and depolymerase activity.
- Inhibition and depletion studies of Plk1 and Aurora A in vivo.
- Immunofluorescence microscopy to analyze microtubule-associated Kif2a signals and spindle microtubule intensity.
Main Results:
- Kif2a was identified as a target of Polo-like kinase 1 (Plk1).
- Plk1 phosphorylates Kif2a, enhancing its depolymerase activity and promoting microtubule destabilization.
- Aurora A also phosphorylates Kif2a, but suppresses its depolymerase activity, leading to microtubule stabilization.
- Antagonistic regulation by Plk1 and Aurora A creates differential microtubule stability within the mitotic spindle.
Conclusions:
- Kif2a activity is tightly controlled by the opposing actions of Plk1 (positive regulator) and Aurora A (negative regulator).
- This antagonistic regulation is essential for establishing spatial differences in microtubule stability, which is critical for accurate spindle assembly and chromosome segregation.
- The findings reveal a novel regulatory mechanism governing microtubule dynamics during mitosis.
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