Stage‐Resolved Phosphoproteomic Landscape of Mouse Spermiogenesis Reveals Key Kinase Signaling in Sperm Morphogenesis

作者：Tianyu Zhu, Yan Zhu, Xinyi Jiang, Xiangzheng Zhang, Bing Wang, Yu Chen, Yichen Zhao, Yulian Wang, Qi Zhou, Zhongyan Han, Yaling Qi, Mengjiao Luo, Haixia Tu, Bingjie Hao, Mengmeng Gao, Jie Ren, Xin Zhou, Xingyu Zhang, Xu Chen, Haojie Li, Qian Huang, Chenghao Situ, Yueshuai Guo, Hui Zhu, Yan Li, Xuejiang Guo · 发表于：Advanced Science · 年份：2025 · DOI：10.1002/advs.202508538 · 被引用次数：4 · 研究领域：Genetic and Kidney Cyst Diseases、Renal and related cancers、Microtubule and mitosis dynamics

Spermiogenesis is the committed step of sperm production, during which spermatid cells undergo dramatic morphological transformations and transcriptional silencing. Post-translational modifications (PTMs), including phosphorylation, provide a level of protein function flexibility and play important roles in spermiogenesis. Dynamic protein phosphorylation profiles of spermatids are characterized across four different developing steps, and identified phosphorylation regulation of key proteins in spermiogenesis. Expression module and kinase-substrate phosphorylation network analysis revealed significant kinase activities of CSNK1G1 and TTBK2. CSNK1G1 is localized in the acrosome and is indispensable for acrosome biogenesis. Ttbk2 male germ cell conditional knockout mice are infertile with flagella development and head shaping defects. TTBK2 is essential for both the phosphorylation and stabilization of IFT88, an intraflagellar transport (IFT) protein with which TTBK2 colocalizes and interacts. Ciliogenesis defects in Ttbk2 knockout cells can be rescued by overexpression of TTBK2 or IFT88 but not kinase-dead TTBK2. Collectively, the systematic profiling of the spermiogenesis phosphoproteome revealed the dynamic nature and important functions of kinase phosphorylation in spermiogenesis and male fertility.