Department of Anatomy and Developmental Biology and Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
University of Rennes, CNRS, IGDR - UMR 6290, F-35000 Rennes, France.
Open Biol. 2023 Mar;13(3):220326. doi: 10.1098/rsob.220326. Epub 2023 Mar 8.
Polo-like kinase I (Plk1) is a highly conserved seronine/threonine kinase essential in meiosis and mitosis for spindle formation and cytokinesis. Here, through temporal application of Plk1 inhibitors, we identify a new role for Plk1 in the establishment of cortical polarity essential for highly asymmetric cell divisions of oocyte meiosis. Application of Plk1 inhibitors in late metaphase I abolishes pPlk1 from spindle poles and prevents the induction of actin polymerization at the cortex through inhibition of local recruitment of Cdc42 and Neuronal Wiskott-Aldrich Syndrome protein (N-WASP). By contrast, an already established polar actin cortex is insensitive to Plk1 inhibitors, but if the polar cortex is first depolymerized, Plk1 inhibitors completely prevent its restoration. Thus, Plk1 is essential for establishment but not maintenance of cortical actin polarity. These findings indicate that Plk1 regulates recruitment of Cdc42 and N-Wasp to coordinate cortical polarity and asymmetric cell division.
丝氨酸/苏氨酸激酶 Polo 样激酶 1(Plk1)在有丝分裂和减数分裂中对纺锤体形成和胞质分裂至关重要,是高度保守的。在这里,通过 Plk1 抑制剂的时间应用,我们确定了 Plk1 在皮质极性建立中的新作用,这对于卵母细胞减数分裂的高度不对称细胞分裂至关重要。在中期 I 晚期应用 Plk1 抑制剂会从纺锤体极中去除 pPlk1,并通过抑制局部募集细胞分裂周期蛋白 42(Cdc42)和神经元 Wiskott-Aldrich 综合征蛋白(N-WASP)来防止皮层处的肌动蛋白聚合的诱导。相比之下,已经建立的极性肌动蛋白皮质对 Plk1 抑制剂不敏感,但是如果首先使极性皮质解聚,Plk1 抑制剂则完全阻止其恢复。因此,Plk1 对于皮质肌动蛋白极性的建立是必需的,但不是维持所必需的。这些发现表明 Plk1 调节 Cdc42 和 N-WASP 的募集以协调皮质极性和不对称细胞分裂。