The slingshot phosphatase 2 is required for acrosome biogenesis during spermatogenesis in mice

  1. Ke Xu
  2. Xianwei Su
  3. Kailun Fang
  4. Yue Lv
  5. Tao Huang
  6. Mengjing Li
  7. Ziqi Wang
  8. Yingying Yin
  9. Tahir Muhammad
  10. Shangming Liu
  11. Xiangfeng Chen
  12. Jing Jiang
  13. Jinsong Li
  14. Wai-Yee Chan
  15. Jinlong Ma
  16. Gang Lu  Is a corresponding author
  17. Zi-Jiang Chen  Is a corresponding author
  18. Hongbin Liu  Is a corresponding author
  1. Shandong University, China
  2. Chinese University of Hong Kong, China
  3. Chinese Academy of Sciences, China
  4. Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, China

Abstract

The acrosome is a membranous organelle positioned in the anterior portion of the sperm head and is essential for male fertility. Acrosome biogenesis requires the dynamic cytoskeletal shuttling of vesicles towards nascent acrosome which is regulated by a series of accessory proteins. However, much remains unknown about the molecular basis underlying this process. Here, we generated Ssh2 knock-out (KO) mice and HA-tagged Ssh2 knock-in (KI) mice to define the functions of Slingshot phosphatase 2 (SSH2) in spermatogenesis and demonstrated that as a regulator of actin remodeling, SSH2 is essential for acrosome biogenesis and male fertility. In Ssh2 KO males, spermatogenesis was arrested at the early spermatid stage with increased apoptotic index and the impaired acrosome biogenesis was characterized by defective transport/fusion of proacrosomal vesicles. Moreover, disorganized F-actin structures accompanied by excessive phosphorylation of COFILIN were observed in the testes of Ssh2 KO mice. Collectively, our data reveal a modulatory role for SSH2 in acrosome biogenesis through COFILIN-mediated actin remodeling and the indispensability of this phosphatase in male fertility in mice.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 1-7 and Figure supplement.

Article and author information

Author details

  1. Ke Xu

    Center for Reproductive Medicine, Shandong University, Jinan, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Xianwei Su

    CUHK-SDU Joint Laboratory on Reproductive Genetics, Chinese University of Hong Kong, Hong Kong, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Kailun Fang

    Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2456-6423
  4. Yue Lv

    Shandong Key Laboratory of Reproductive Medicine, Shandong University, Jinan, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Tao Huang

    Center for Reproductive Medicine, Shandong University, Jinan, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7086-570X
  6. Mengjing Li

    Center for Reproductive Medicine, Shandong University, Jinan, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Ziqi Wang

    Center for Reproductive Medicine, Shandong University, Jinan, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Yingying Yin

    Center for Reproductive Medicine, Shandong University, Jinan, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Tahir Muhammad

    Center for Reproductive Medicine, Shandong University, Jinan, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Shangming Liu

    School of Basic Medical Sciences, Shandong University, Jinan, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Xiangfeng Chen

    Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Jing Jiang

    Shanghai Institute of Biochemistry and Cell Biolog, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  13. Jinsong Li

    Shanghai Institute of Biochemistry and Cell Biolog, Chinese Academy of Sciences, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3456-662X
  14. Wai-Yee Chan

    CUHK-SDU Joint Laboratory on Reproductive Genetics, Chinese University of Hong Kong, Hong Kong, China
    Competing interests
    The authors declare that no competing interests exist.
  15. Jinlong Ma

    Center for Reproductive Medicine, Shandong University, Jinan, China
    Competing interests
    The authors declare that no competing interests exist.
  16. Gang Lu

    CUHK-SDU Joint Laboratory on Reproductive Genetics, Chinese University of Hong Kong, Hong Kong, China
    For correspondence
    lugang@cuhk.edu.hk
    Competing interests
    The authors declare that no competing interests exist.
  17. Zi-Jiang Chen

    Center for Reproductive Medicine, Shandong University, Jinan, China
    For correspondence
    chenzijiang@hotmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6637-6631
  18. Hongbin Liu

    Center for Reproductive Medicine, Shandong University, Jinan, China
    For correspondence
    hongbin_sduivf@aliyun.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2550-7492

Funding

National Key Research and Development Program of China (2021YFC2700500)

  • Jinlong Ma

National Natural Science Foundation of China (82071699)

  • Hongbin Liu

National Natural Science Foundation of China (81771538)

  • Hongbin Liu

National Key Research and Development Program of China (2022YFC2702600)

  • Hongbin Liu

Chinese Academy of Medical Sciences (2020RU001)

  • Zi-Jiang Chen

Shandong First Medical University (Academic Promotion Programme,2019U001)

  • Zi-Jiang Chen

Major Scientific and Technological Innovation Project of Shandong Province (2021ZDSYS16)

  • Hongbin Liu

Natural Science Fund for Distinguished Young Scholars of Shandong Province (ZR2021JQ27)

  • Hongbin Liu

Taishan Scholar Project of Shandong Province (Program for Young Experts,tsqn202103192)

  • Hongbin Liu

National Natural Science Foundation of China (Basic Science Center Program,31988101)

  • Zi-Jiang Chen

Key Technology Research and Development Program of Shandong (2020ZLYS02)

  • Zi-Jiang Chen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Wei Yan, University of California, Los Angeles, United States

Ethics

Animal experimentation: All procedures were in accordance with the ethical standards approved by the Animal Use Committee of the School of Medicine, Shandong University, for the care and use of laboratory animals. The research was approved by the Institutional Review Board of Shandong University. (Reference Number: 2019#057).

Version history

  1. Received: September 1, 2022
  2. Preprint posted: September 17, 2022 (view preprint)
  3. Accepted: March 20, 2023
  4. Accepted Manuscript published: March 21, 2023 (version 1)
  5. Version of Record published: March 31, 2023 (version 2)

Copyright

© 2023, Xu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Ke Xu
  2. Xianwei Su
  3. Kailun Fang
  4. Yue Lv
  5. Tao Huang
  6. Mengjing Li
  7. Ziqi Wang
  8. Yingying Yin
  9. Tahir Muhammad
  10. Shangming Liu
  11. Xiangfeng Chen
  12. Jing Jiang
  13. Jinsong Li
  14. Wai-Yee Chan
  15. Jinlong Ma
  16. Gang Lu
  17. Zi-Jiang Chen
  18. Hongbin Liu
(2023)
The slingshot phosphatase 2 is required for acrosome biogenesis during spermatogenesis in mice
eLife 12:e83129.
https://doi.org/10.7554/eLife.83129

Share this article

https://doi.org/10.7554/eLife.83129

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