P190RhoGAP prevents mitotic spindle fragmentation and is required to activate Aurora A kinase at acentriolar poles
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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.
Keywordsp190RhoGAP Mitotic spindle Aurora A Centrosome Eg5
The authors would like to thank Anindya Dutta for the interim support that was crucial for this work.
This study was supported by NIH R01 GM118798.
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Conflict of interest
The authors declare that they have no conflict of interest.
There were no animals used in this study. This article does not contain any studies with human participants performed by any of the authors.
- van Heesbeen RG, Raaijmakers JA, Tanenbaum ME, Halim VA, Lelieveld D, Lieftink C, Heck AJ,Egan DA, Medema RH (2017) Aurora A, MCAK, and Kif18b promote Eg5-independent spindle formation. Chromosoma 126(4):473–486Google Scholar
- Zhao J, Xu H, He M, Wang Z, Wu Y (2014) Rho GTPase-activating protein 35rs1052667 polymorphism and osteosarcoma risk and prognosis. Biomed Res Int 2014:396947. https://doi.org/10.1155/2014/396947