The highly evolutionarily conserved protein phosphatase 6 (PP6) has been shown to have a role in many cellular processes, including the cell cycle. PP6 modulates Aurora A activity in mitosis; however, its role in meiosis is completely unknown. To understand the function of PP6 in reproductive cells, Qing-Yuan Sun, Xiao Yang, Xingzhi Xu and colleagues (p. ) generated and analysed conditional knockout (KO) mice in which the catalytic subunit of PP6 (PPP6C) had been deleted (Ppp6F/F;Zp3-Cre). Ppp6c conditional KO mice were subfertile, but both follicular development and completion of meiosis I were unaffected by Ppp6c ablation. Upon inspection of Ppp6c conditional KO embryos, the authors found a high incidence of aneuploidy with a failure to reach the blastocyst stage and defects in second polar body extrusion, as well as in pronuclei formation. Close examination of Ppp6c conditional KO oocytes revealed abnormal microtubule spindles and a lack of the contractile ring, which resulted in incomplete cytokinesis, indicating that PP6 is indispensable for exit from meiosis II. Consistent with PP6-mediated dephosphorylation of Aurora A at residue T288 in mitosis, the authors found that the levels of Aurora A phosphorylated at T288 were increased in PPP6C-depleted oocytes. Finally, pharmacological inhibition of Aurora A rescued spindle defects and significantly improved pronuclei formation in Ppp6c conditional KO oocytes. Taken together, the data presented here demonstrate that PP6, by acting on its main substrate Aurora A, is required for the exit of oocytes from meiosis II.
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