Pnma5 is essential to the progression of meiosis in mouse oocytes through a chain of phosphorylation
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Xiao-Lan Zhang1,*, Peng Liu1,*, Zhi-Xia Yang1,*, Jing-Jing Zhao3, Lei-Lei Gao1, Bo Yuan4, Li-Ya Shi1, Chun-Xiang Zhou1, Hai-Feng Qiao5, Ya-Hong Liu6, Xiao-Yan Ying6, Jun-Qiang Zhang2, Xiu-Feng Ling2 and Dong Zhang1
1State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China
2Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, China
3Department of Veterinary Drug Supervision, Taiyuan, Shanxi, China
4Wenxi Agriculture Committee, Yuncheng, Shanxi, China
5Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
6Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China
*These authors have contributed equally to this work
Dong Zhang, email: [email protected]
Xiu-Feng Ling, email: [email protected]
Keywords: Pnma5, meiosis, oocytes, fertilization, phosphorylation
Received: December 22, 2016 Accepted: May 03, 2017 Published: June 09, 2017
PNMA (paraneoplastic antigen MA) family includes Pnma1–6. Although other members have been found to be involved in paraneoplastic neurological disorders, death receptor-dependent apoptosis, and tumorigenesis, Pnma5 was thought to be a female fertility factor, as indicated by one genome-wide study. But until now there have not been any further functional studies about Pnma5 in female meiosis. Our preliminary study indicated that Pnma5 might play important roles in meiosis. To further address this, Pnma5 was knocked down in in-vitro maturated (IVM) mouse oocytes, which are common models for mammalian female meiosis, by specific siRNA, and results showed that the loss of Pnma5 significantly delayed the progression of meiosis I and increased chromosome segregation errors during anaphase I. In in-vitro fertilization (IVF), Pnma5 knockdown caused significantly lower fertilization. To assess how it affects meiosis, Pnma5 knockdown was found to significantly decrease the stability of spindle microtubules and altered F-actin organization within actin cap regions, cause significantly abnormal mitochondria aggregation and lower ATP concentration. Next we have found that phosphorylation at Thr533 re-located Pnma5 strongly to spindles & cortex and was required for the phosphorylation of Akt and Gsk3β, while Src and Erk1/2 phosphorylation was required for the phosphorylation of Pnma5, indicating that phosphorylated Pnma5 is the active form and subsequently activates Akt and Gsk3β. Collectively this study suggests that Pnma5 is important for meiosis and is the pivot of Src→Erk1/2→Pnma5→Akt→Gsk3β pathway.
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