期刊
CELL CYCLE
卷 14, 期 24, 页码 3908-3919出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2015.1120920
关键词
gamma-actin; abnormal mitotic spindles; centrosome amplification; mitosis; mitotic abnormalities; mitotic progression
类别
资金
- Children's Cancer Institute Australia
- Kids' Cancer Project
- National Health and Medical Research Council Fellowship [1058299]
- Cancer Council New South Wales Program Grant
- Australian Research Council Center of Excellence in Convergent Bio-Nano Science and Technology [CE140100036]
- National Health and Medical Research Council of Australia [1058299] Funding Source: NHMRC
Reorganization of the actin cytoskeleton during mitosis is crucial for regulating cell division. A functional role for -actin in mitotic arrest induced by the microtubule-targeted agent, paclitaxel, has recently been demonstrated. We hypothesized that -actin plays a role in mitosis. Herein, we investigated the effect of -actin in mitosis and demonstrated that -actin is important in the distribution of -actin and formation of actin-rich retraction fibers during mitosis. The reduced ability of paclitaxel to induce mitotic arrest as a result of -actin depletion was replicated with a range of mitotic inhibitors, suggesting that -actin loss reduces the ability of broad classes of anti-mitotic agents to induce mitotic arrest. In addition, partial depletion of -actin enhanced centrosome amplification in cancer cells and caused a significant delay in prometaphase/metaphase. This prolonged prometaphase/metaphase arrest was due to mitotic defects such as uncongressed and missegregated chromosomes, and correlated with an increased presence of mitotic spindle abnormalities in the -actin depleted cells. Collectively, these results demonstrate a previously unknown role for -actin in regulating centrosome function, chromosome alignment and maintenance of mitotic spindle integrity.
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