In:
Journal of Cell Science, The Company of Biologists
Abstract:
Dynamic protein phosphorylation and dephosphorylation, mediated by a conserved cohort of protein kinases or phosphatases, regulate cell cycle progression. Among the well-known PP2A-like protein phosphatases, PP6 has been analyzed in mammalian mitosis recently identifying Aurora A as its key substrate. However, the functions of PP6 in meiosis are still entirely unknown. To identify the physiological role of PP6 in female gametogenesis, Ppp6cF/F mice were first generated and crossed with Zp3-Cre mice to selectively disrupt Ppp6c expression in oocytes. Here we report for the first time that PP6c was dispensable for oocyte meiotic maturation but essential for MII exit after fertilization, since depletion of PP6c caused abnormal MII spindle and disrupted MII cytokinesis, resulting in zygotes with high risk of aneuploidy, defective early embryonic development, thus severe subfertility. We also revealed that PP6 inactivation interfered with MII spindle formation and MII exit due to increased Aurora A activity, and Aurora A inhibition with MLN8237 could rescue the PP6c depletion phenotype. In conclusion, our findings uncover a hitherto unknown role for PP6 as an indispensable regulator of oocyte meiosis and female fertility.
Type of Medium:
Online Resource
ISSN:
1477-9137
,
0021-9533
Language:
English
Publisher:
The Company of Biologists
Publication Date:
2015
detail.hit.zdb_id:
219171-4
detail.hit.zdb_id:
1483099-1
SSG:
12
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