2. Academic Validation
  3. The global phosphorylation landscape of mouse oocytes during meiotic maturation

The global phosphorylation landscape of mouse oocytes during meiotic maturation

  • EMBO J. 2024 Oct;43(20):4752-4785. doi: 10.1038/s44318-024-00222-1.
Hongzheng Sun # 1,  Longsen Han # 1,  Yueshuai Guo # 1,  Huiqing An # 1,  Bing Wang # 1,  Xiangzheng Zhang 1,  Jiashuo Li 1,  Yingtong Jiang 1,  Yue Wang 1,  Guangyi Sun 1,  Shuai Zhu 1,  Shoubin Tang 1,  Juan Ge 1,  Minjian Chen 1,  Xuejiang Guo 2 3,  Qiang Wang 4 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Reproductive Medicine and Offspring Health, Changzhou Maternity and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, 211166, Nanjing, China.
  • 2 State Key Laboratory of Reproductive Medicine and Offspring Health, Changzhou Maternity and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, 211166, Nanjing, China. guo_xuejiang@njmu.edu.cn.
  • 3 Department of Histology and Embryology, Nanjing Medical University, 211166, Nanjing, China. guo_xuejiang@njmu.edu.cn.
  • 4 State Key Laboratory of Reproductive Medicine and Offspring Health, Changzhou Maternity and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, 211166, Nanjing, China. qwang2012@njmu.edu.cn.
  • 5 Center for Global Health, School of Public Health, Nanjing Medical University, 211166, Nanjing, China. qwang2012@njmu.edu.cn.
  • # Contributed equally.
PMID: 39256562 DOI: 10.1038/s44318-024-00222-1
Abstract

Phosphorylation is a key post-translational modification regulating protein function and biological outcomes. However, the phosphorylation dynamics orchestrating mammalian oocyte development remains poorly understood. In the present study, we apply high-resolution mass spectrometry-based phosphoproteomics to obtain the first global in vivo quantification of mouse oocyte phosphorylation. Of more than 8000 phosphosites, 75% significantly oscillate and 64% exhibit marked upregulation during meiotic maturation, indicative of the dominant regulatory role. Moreover, we identify numerous novel phosphosites on oocyte proteins and a few highly conserved phosphosites in oocytes from different species. Through functional perturbations, we demonstrate that phosphorylation status of specific sites participates in modulating critical events including metabolism, translation, and RNA processing during meiosis. Finally, we combine inhibitor screening and enzyme-substrate network prediction to discover previously unexplored kinases and phosphatases that are essential for oocyte maturation. In sum, our data define landscape of the oocyte phosphoproteome, enabling in-depth mechanistic insights into developmental control of germ cells.

Keywords

Kinase; Meiosis; Oocyte; Phosphatase; Phosphorylation.

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