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
  • 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: [email protected].
  • 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: [email protected].
  • 6. Department of Histology and Embryology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China. Electronic address: [email protected].
PMID: 40885374 DOI: 10.1016/j.mce.2025.112645
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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