睾丸特异性丝氨酸/苏氨酸激酶dTSSK2调节果蝇的精子活力和雄性生育力。

Testis-specific serine/threonine kinase dTSSK2 regulates sperm motility and male fertility in Drosophila.

作者信息

Peng Ju, Sun Angyang, Zheng Jie, Zhang Na, Zhang Xuedi, Gao Guanjun

机构信息

School of Life Science and Technology, ShanghaiTech University, Shanghai, China.

School of Basic Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu Province, China.

出版信息

Commun Biol. 2025 May 8;8(1):710. doi: 10.1038/s42003-025-08163-z.

DOI:10.1038/s42003-025-08163-z

PMID:40335644

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12059139/

Abstract

Serine/threonine kinases of the TSSK (Testis-Specific Serine/Threonine Kinase) family play crucial roles in spermatogenesis and male fertility across species, but the underlying regulatory mechanism remains incompletely understood. In this study, we identified and characterized a novel TSSK homolog in Drosophila, named dTSSK2 (CG9222), which functions as the ortholog of human TSSK4. dTSSK2 is specifically expressed in the testis and localizes to individualization complexes during spermiogenesis. Disruption of dTSSK2 severely compromises sperm motility, leading to failed sperm transit into the seminal vesicle and male infertility. Phosphoproteomic analyses reveal that dTSSK2 coordinates sperm flagella assembly and motility by phosphorylating proteins involved in microtubule organization, organelle assembly, and flagella structure. Notably, dTSSK2 phosphorylates the substrate Gudu at Ser9, which partially contributes to individualization complex integrity and sperm motility. These findings elucidate the critical role of dTSSK2-mediated phosphorylation in regulating Drosophila male fertility.

摘要

TSSK（睾丸特异性丝氨酸/苏氨酸激酶）家族的丝氨酸/苏氨酸激酶在物种间的精子发生和雄性生育中发挥着关键作用，但其潜在的调控机制仍未完全清楚。在本研究中，我们在果蝇中鉴定并表征了一种新的TSSK同源物，命名为dTSSK2（CG9222），它作为人类TSSK4的直系同源物发挥作用。dTSSK2在睾丸中特异性表达，并在精子发生过程中定位于个体化复合体。dTSSK2的破坏严重损害精子活力，导致精子无法进入精囊并造成雄性不育。磷酸蛋白质组学分析表明，dTSSK2通过磷酸化参与微管组织、细胞器组装和鞭毛结构的蛋白质来协调精子鞭毛的组装和活力。值得注意的是，dTSSK2在Ser9位点磷酸化底物Gudu，这部分有助于个体化复合体的完整性和精子活力。这些发现阐明了dTSSK2介导的磷酸化在调节果蝇雄性生育中的关键作用。