title: 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.affiliation: a Children's Cancer Institute; Lowy Cancer Research Center; University of New South Wales ; Randwick , NSW , Australia.
authors.forename: Sela T
authors.initials: ST
authors.lastname: Po'uha
authors.affiliation: a Children's Cancer Institute; Lowy Cancer Research Center; University of New South Wales ; Randwick , NSW , Australia.|b ARC Center of Excellence in Convergent Bio-Nano Science and Technology; Australian Center for Nanomedicine; University of New South Wales ; Sydney , Australia.
authors.forename: Maria
authors.initials: M
authors.lastname: Kavallaris
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D018385:Centrosome / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D008677:Metaphase / Q000235:genetics / Q000502:physiology; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D008941:Spindle Apparatus / Q000378:metabolism; D014404:Tubulin / Q000235:genetics / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D014404:Tubulin
keywords: abnormal mitotic spindles; centrosome amplification; mitosis; mitotic abnormalities; mitotic progression; γ-actin