Aurora A kinase modulates actin cytoskeleton through phosphorylation of Cofilin: Implication in the mitotic process

Abstract

Aurora A kinase regulates early mitotic events through phosphorylation and activation of a variety of proteins. Specifically, Aur-A is involved in centrosomal separation and formation of mitotic spindles in early prophase. The effect of Aur-A on mitotic spindles is mediated by the modulation of microtubule dynamics and association with microtubule binding proteins. In this study we show that Aur-A exerts its effects on spindle organization through the regulation of the actin cytoskeleton. Aurora A phosphorylates Cofilin at multiple sites including S3 resulting in the inactivation of its actin depolymerizing function. Aur-A interacts with Cofilin in early mitotic phases and regulates its phosphorylation status. Cofilin phosphorylation follows a dynamic pattern during the progression of prophase to metaphase. Inhibition of Aur-A activity induced a delay in the progression of prophase to metaphase. Aur-A inhibitor also disturbed the pattern of Cofilin phosphorylation, which correlated with the mitotic delay. Our results establish a novel function of Aur-A in the regulation of actin cytoskeleton reorganization, through Cofilin phosphorylation during early mitotic stages.

Aurora-A Breaks Symmetry in Contractile Actomyosin Networks Independently of Its Role in Centrosome Maturation

“…In addition, AIR-1 may target PAR-2, a RING-finger protein that directly associates with plasma membrane lipids (Motegi et al, 2011) and antagonizes cortical recruitment of NMY-2 (Zonies et al, 2010). In other organisms, Aurora-A has been shown to phosphorylate and inhibit Rho-kinase in Drosophila (Moon and Matsuzaki, 2013) and modulate the level of cofilin phosphorylation during breast tumor metastasis (Ritchey and Chakrabarti, 2014). Therefore, it is possible that AIR-1 may phosphorylate these effectors in the RHO-1 pathway, which then contribute to the modification of RHO-1 activity through unknown feedback pathways.…”

Effects of PAK4/LIMK1/Cofilin‐1 signaling pathway on proliferation, invasion, and migration of human osteosarcoma cells

“…and was phosphorylated by regulating actin recombination with LMK1 to accelerate the cell cycle progress and promote cell proliferation. 30,31 As indicated by Guo B et al, after inhibition of PAK4, the proliferation of lung adenocarcinoma cells was restricted, with the arrested cell cycle at the G1 phase and the promoted early apoptosis of lung adenocarcinoma cells. 32 Also, the inhibited PAK4/LIMK1/ Cofilin pathway resulted in the cell cycle arrest at the G1 phase and the declined cell proliferation in accordance with the study of Jian Zhang et al 33 Additionally, LIMK1/Cofilin pathway modulates cytoskeletal dynamics to affect the formation of microfilament actin stress fibers and adhesion plaque, eventually influencing the metastasis behavior of tumor cells.…”

Coupling changes in cell shape to chromosome segregation

“…For example, phosphorylationinduced changes in the activities of proteins that negatively regulate actin fila ment formation, including LIM kinase, cofilin and WD repeatcontaining protein 1 (WDR1), may contribute to an increase in the actin filament turnover rate upon entry into mitosis 35,[47][48][49][50] . Furthermore, the activation of actin filamentbinding proteins, such as ERM (Ezrin, Radixin, Moesin) proteins, brought about by the SLIK kinase 51,52 leads to the physical crosslinking of the actin filaments to proteins embedded in the plasma mem brane 52,53 (FIG.…”