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Broad phosphorylation mediated by testis-specific serine/threonine kinases contributes to spermiogenesis and male fertility

Author

Listed:
  • Xuedi Zhang

    (ShanghaiTech University)

  • Ju Peng

    (ShanghaiTech University)

  • Menghua Wu

    (ShanghaiTech University
    Tsinghua University)

  • Angyang Sun

    (ShanghaiTech University)

  • Xiangyu Wu

    (ShanghaiTech University)

  • Jie Zheng

    (ShanghaiTech University)

  • Wangfei Shi

    (ShanghaiTech University)

  • Guanjun Gao

    (ShanghaiTech University)

Abstract

Genetic studies elucidate a link between testis-specific serine/threonine kinases (TSSKs) and male infertility in mammals, but the underlying mechanisms are unclear. Here, we identify a TSSK homolog in Drosophila, CG14305 (termed dTSSK), whose mutation impairs the histone-to-protamine transition during spermiogenesis and causes multiple phenotypic defects in nuclear shaping, DNA condensation, and flagellar organization in spermatids. Genetic analysis demonstrates that kinase catalytic activity of dTSSK, which is functionally conserved with human TSSKs, is essential for male fertility. Phosphoproteomics identify 828 phosphopeptides/449 proteins as potential substrates of dTSSK enriched primarily in microtubule-based processes, flagellar organization and mobility, and spermatid differentiation and development, suggesting that dTSSK phosphorylates various proteins to orchestrate postmeiotic spermiogenesis. Among them, the two substrates, protamine-like protein Mst77F/Ser9 and transition protein Mst33A/Ser237, are biochemically validated to be phosphorylated by dTSSK in vitro, and are genetically demonstrated to be involved in spermiogenesis in vivo. Collectively, our findings demonstrate that broad phosphorylation mediated by TSSKs plays an indispensable role in spermiogenesis.

Suggested Citation

  • Xuedi Zhang & Ju Peng & Menghua Wu & Angyang Sun & Xiangyu Wu & Jie Zheng & Wangfei Shi & Guanjun Gao, 2023. "Broad phosphorylation mediated by testis-specific serine/threonine kinases contributes to spermiogenesis and male fertility," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38357-0
    DOI: 10.1038/s41467-023-38357-0
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    1. James B. Brown & Nathan Boley & Robert Eisman & Gemma E. May & Marcus H. Stoiber & Michael O. Duff & Ben W. Booth & Jiayu Wen & Soo Park & Ana Maria Suzuki & Kenneth H. Wan & Charles Yu & Dayu Zhang &, 2014. "Diversity and dynamics of the Drosophila transcriptome," Nature, Nature, vol. 512(7515), pages 393-399, August.
    2. Saher Sue Hammoud & David A. Nix & Haiying Zhang & Jahnvi Purwar & Douglas T. Carrell & Bradley R. Cairns, 2009. "Distinctive chromatin in human sperm packages genes for embryo development," Nature, Nature, vol. 460(7254), pages 473-478, July.
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