Supervillin Isoform 4 (SV4) Regulates Mitosis by Enhancing Aurora A Activity
10.13865/j.cnki.cjbmb.2023.10.1293
- Author:
Wen-Xu BI
1
;
Si-Yu ZHANG
1
;
Shu-Yang LI
1
;
Wei WANG
1
;
Xue-Ran CHEN
1
;
Zhi-You FANG
1
;
Wen-Xu BI
2
;
Si-Yu ZHANG
2
;
Xue-Ran CHEN
2
;
Zhi-You FANG
2
Author Information
1. Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences
2. Basic Medical Science Research Center, Institute of Health and Medical Technology, Science Island Branch, Graduate School of University of Science and Technology of China
- Publication Type:Journal Article
- Keywords:
Aurora A;
centrosome;
microtubule;
mitosis;
supervillin
- From:
Chinese Journal of Biochemistry and Molecular Biology
2023;39(11):1588-1597
- CountryChina
- Language:Chinese
-
Abstract:
Mitosis is important for cell proliferation in eukaryotes, and chromosome replication and accurate separation are essential for cell division. Supervillin is a membrane and microfilament actin binding protein. Previous studies have found that it regulates the dynamic changes of the cortical distribution of F-actin and myosin II in cytokinesis, thus ensuring the correct distribution of the contraction ring and participating in the final completion of cytoplasm divisions. But it is not clear whether it functions during metaphase. Supervillin has several splicing isomers, among which supervillin isoform 4 (SV4) is the largest splicing isomer. In this study, the expression of SV4 in cells was reduced by the RNA interference method, and the dynamic process of mitosis and the morphology of astral spindles were detected and observed by real-time microscopy and immunofluorescence staining, and the potential molecular mechanism of SV4 in mitosis was analyzed. The results showed abnormal cell divisions after SV4 reduction: delayed transition from metaphase to anaphase (P<0.001), abnormal assembly of microtubules, a twofold-increase of the number of cells with multipolar spindles, and decreased γ-tubulin signaling in the centrosome (P<0.001). Through GST pull-down and mass spectrometry experiments, we found that SV4 and Aurora A bind to each other, and SV4 regulates the localization and activation of Aurora A in the centrosome during mitosis. In summary, supervillin plays an important role in mitosis. The isomer SV4 regulates spindle integrity and γ-tubulin recruitment by interacting with Aurora A and recruiting it for proper localization and activation in the centrosome during the metaphase, thus promoting the correct assembly of bipolar spindles and ensuring the accurate separation of chromosomes and the smooth progress of mitosis.
