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Published on: September 20, 2019
Aurora B regulates formin mDia3 in achieving metaphase chromosome alignment
Lina Cheng1, Jiayin Zhang, Sana Ahmad
1Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
The formin mDia3 protein is crucial for aligning chromosomes during cell division by interacting with microtubules. Aurora B kinase phosphorylation of mDia3 regulates this process, ensuring accurate chromosome segregation.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Accurate chromosome segregation during mitosis relies on correct kinetochore-spindle attachments.
- The formin mDia3 protein has been implicated in various cellular processes, but its specific role in mitosis remains unclear.
Purpose of the Study:
- To investigate the role of the formin mDia3 in chromosome alignment during mitosis.
- To determine the mechanism by which mDia3 contributes to proper kinetochore-microtubule interactions.
Main Methods:
- Utilized mDia3 mutants (nonphosphorylatable and phosphomimetic) in cell-based assays.
- Performed in vitro binding and microtubule stabilization assays with purified mDia3 and Aurora B kinase.
- Analyzed chromosome alignment and kinetochore-microtubule fiber formation in treated cells.
Main Results:
- mDia3 is essential for metaphase chromosome alignment, independent of its actin nucleation activity.
- EB1-binding by mDia3 is critical for its function in chromosome alignment.
- Aurora B kinase phosphorylation of mDia3's FH2 domain reduces its microtubule-binding and stabilizing abilities.
- Cells with nonphosphorylatable mDia3 fail to position chromosomes correctly, while phosphomimetic mutants show unstable kinetochore fibers.
Conclusions:
- mDia3 plays a key role in establishing stable kinetochore-microtubule attachments for accurate chromosome segregation.
- Regulation of mDia3 by Aurora B phosphorylation is critical for its function in mitosis.
- These findings elucidate a novel mechanism for mitotic spindle-kinetochore interaction control.
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