Gamma-actin is involved in regulating centrosome function and mitotic progression in cancer cells.

Abstract

Reorganization of the actin cytoskeleton during mitosis is crucial for regulating cell division. A functional role for γ-actin in mitotic arrest induced by the microtubule-targeted agent, paclitaxel, has recently been demonstrated. We hypothesized that γ-actin plays a role in mitosis. Herein, we investigated the effect of γ-actin in mitosis and demonstrated that γ-actin is important in the distribution of β-actin and formation of actin-rich retraction fibers during mitosis. The reduced ability of paclitaxel to induce mitotic arrest as a result of γ-actin depletion was replicated with a range of mitotic inhibitors, suggesting that γ-actin loss reduces the ability of broad classes of anti-mitotic agents to induce mitotic arrest. In addition, partial depletion of γ-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 γ-actin depleted cells. Collectively, these results demonstrate a previously unknown role for γ-actin in regulating centrosome function, chromosome alignment and maintenance of mitotic spindle integrity.

• Authors: Sela T Po'uha, Maria Kavallaris
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 14 Issue 24 Pg. 3908-19 ( 2015) ISSN: 1551-4005 [Electronic] United States
• PMID: 26697841 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Small Interfering
• Tubulin

Topics

• Cell Cycle (genetics)
• Centrosome (metabolism)
• Humans
• MCF-7 Cells
• Metaphase (genetics, physiology)
• Microscopy, Fluorescence
• Microtubules (metabolism)
• Mitosis (genetics, physiology)
• RNA, Small Interfering (genetics)
• Spindle Apparatus (metabolism)
• Tubulin (genetics, metabolism)