1. Academic Validation
  2. The N-terminal region of HASPIN regulates phosphorylation of AURKA and meiotic progression in spermatocytes

The N-terminal region of HASPIN regulates phosphorylation of AURKA and meiotic progression in spermatocytes

  • Mol Cell Endocrinol. 2025 Aug 28:609:112645. doi: 10.1016/j.mce.2025.112645.
Haojie Li 1 Yaoting Xu 2 Xinyi Jiang 2 Jie Ren 3 Yulian Wang 2 Xiangzheng Zhang 2 Mengmeng Gao 2 Longsheng Zhang 2 Yue Wang 2 Zongze Li 2 Suwei Wang 2 Tianye Wang 2 Mengyi Wang 2 Chenghao Situ 4 Xuejiang Guo 5 Hui Zhu 6
Affiliations

Affiliations

  • 1 Medical Research Center, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, 213023, China.
  • 2 Department of Histology and Embryology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China; State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Histology and Embryology, Nanjing Medical University, Nanjing, 211166, China.
  • 3 Reproductive Medicine Center, The First People's Hospital of Lianyungang, Lianyungang, 222061, China.
  • 4 Department of Histology and Embryology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China; State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Histology and Embryology, Nanjing Medical University, Nanjing, 211166, China. Electronic address: situchenghao@njmu.edu.cn.
  • 5 Department of Histology and Embryology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China; State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Histology and Embryology, Nanjing Medical University, Nanjing, 211166, China. Electronic address: guo_xuejiang@njmu.edu.cn.
  • 6 Department of Histology and Embryology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China. Electronic address: njzhuhui@njmu.edu.cn.
Abstract

Protein phosphorylation is an important post-translational modification that plays a critical regulatory role in meiosis. HASPIN, a kinase highly conserved from yeast to mammals, is required for male fertility. In this study, we found that the intrinsically disordered N-terminal domain of HASPIN is also required for this function. Mice with deletion of N-terminal Amino acids (aa) 1-243 of HASPIN exhibited reduced testicular size, sperm count, and fertility. Using immunoprecipitation-mass spectrometry and phosphoproteomics analysis, we found that HASPIN could interact with AURKA and regulate its phosphorylation at T279 via its N-terminus. Taken together, our results suggest that the N-terminus of HASPIN regulates AURKA kinase activity to affect male fertility.

Keywords

Aurora A kinase (AURKA); HASPIN; Meiosis; Phosphoproteome; Spermatocyte.

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