The slingshot phosphatase 2 is required for acrosome biogenesis during spermatogenesis in mice
- Shandong University, China
- Chinese University of Hong Kong, China
- Chinese Academy of Sciences, China
- 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
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
- 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
- Received: September 1, 2022
- Preprint posted: September 17, 2022 (view preprint)
- Accepted: March 20, 2023
- Accepted Manuscript published: March 21, 2023 (version 1)
- 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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The slingshot phosphatase 2 is required for acrosome biogenesis during spermatogenesis in mice
eLife 12:e83129.
https://doi.org/10.7554/eLife.83129
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