title: ZP3 is Required for Germinal Vesicle Breakdown in Mouse Oocyte Meiosis.
abstract: ZP3 is a principal component of the zona pellucida (ZP) of mammalian oocytes and is essential for normal fertility, and knockout of ZP3 causes complete infertility. ZP3 promotes fertilization by recognizing sperm binding and activating the acrosome reaction; however, additional cellular roles for ZP3 in mammalian oocytes have not been yet reported. In the current study, we found that ZP3 was strongly expressed in the nucleus during prophase and gradually translocated to the ZP. Knockdown of ZP3 by a specific siRNA dramatically inhibited germinal vesicle breakdown (GVBD) (marking the beginning of meiosis), significantly reducing the percentage of MII oocytes. To investigate the ZP3-mediated mechanisms governing GVBD, we identified potential ZP3-interacting proteins by immunoprecipitation and mass spectrometry. We identified Protein tyrosine phosphatase, receptor type K (Ptprk), Aryl hydrocarbon receptor-interacting protein-like 1 (Aipl1), and Diaphanous related formin 2 (Diaph2) as potential candidates, and established a working model to explain how ZP3 affects GVBD. Finally, we provided preliminary evidence that ZP3 regulates Akt phosphorylation, lamin binding to the nuclear membrane via Aipl1, and organization of the actin cytoskeleton via Diaph2. These findings contribute to our understanding of a novel role played by ZP3 in GVBD.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Lei-Lei
authors.initials: LL
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Chun-Xiang
authors.initials: CX
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Xiao-Lan
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Gang-Yi
authors.initials: GY
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Zhi-Xia
authors.initials: ZX
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D034882:Lamins / Q000378:metabolism; D008540:Meiosis; D008813:Mice, Inbred ICR; D009865:Oocytes / Q000166:cytology* / Q000378:metabolism*; D010766:Phosphorylation; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D008941:Spindle Apparatus; D015044:Zona Pellucida / Q000378:metabolism; D000072216:Zona Pellucida Glycoproteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C498604:Aipl1 protein, mouse; D002352:Carrier Proteins; D034882:Lamins; D000072216:Zona Pellucida Glycoproteins; C000606521:Zp3 protein, mouse; D051057:Proto-Oncogene Proteins c-akt