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Chromosoma

, Volume 127, Issue 3, pp 375–386 | Cite as

P190RhoGAP prevents mitotic spindle fragmentation and is required to activate Aurora A kinase at acentriolar poles

  • Arkadi Manukyan
  • Lilit Sargsyan
  • Sarah J. Parsons
  • P. Todd Stukenberg
Original Article

Abstract

Assembly of the mitotic spindle is essential for proper chromosome segregation during mitosis. Maintenance of spindle poles requires precise regulation of kinesin- and dynein-generated forces, and improper regulation of these forces disrupts pole integrity leading to pole fragmentation. The formation and function of the mitotic spindle are regulated by many proteins, including Aurora A kinase and the motor proteins Kif2a and Eg5. Here, we characterize a surprising role for the RhoA GTPase-activating protein, p190RhoGAP, in regulating the mitotic spindle. We show that cells depleted of p190RhoGAP arrest for long periods in mitosis during which cells go through multiple transitions between having bipolar and multipolar spindles. Most of the p190RhoGAP-depleted cells finally achieve a stable bipolar attachment and proceed through anaphase. The multipolar spindle phenotype can be rescued by low doses of an Eg5 inhibitor. Moreover, we show that p190RhoGAP-depleted multipolar cells localize Aurora A to all the poles, but the kinase is only activated at the two centriolar poles. Overall, our data identify an unappreciated connection between p190RhoGAP and the proteins that control spindle poles including Aurora A kinase and Eg5 that is required to prevent or correct spindle pole fragmentation.

Keywords

p190RhoGAP Mitotic spindle Aurora A Centrosome Eg5 

Notes

Acknowledgements

The authors would like to thank Anindya Dutta for the interim support that was crucial for this work.

Funding information

This study was supported by NIH R01 GM118798.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approvals

There were no animals used in this study. This article does not contain any studies with human participants performed by any of the authors.

Supplementary material

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Arkadi Manukyan
    • 1
  • Lilit Sargsyan
    • 1
  • Sarah J. Parsons
    • 2
  • P. Todd Stukenberg
    • 1
    • 3
  1. 1.Department of Biochemistry and Molecular GeneticsUniversity of VirginiaCharlottesvilleUSA
  2. 2.Department of Microbiology, Immunology and Cancer BiologyUniversity of VirginiaCharlottesvilleUSA
  3. 3.CharlottesvilleUSA

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