eLife (Mar 2023)
The Slingshot phosphatase 2 is required for acrosome biogenesis during spermatogenesis in mice
- Ke Xu,
- Xianwei Su,
- Kailun Fang,
- Yue Lv,
- Tao Huang,
- Mengjing Li,
- Ziqi Wang,
- Yingying Yin,
- Tahir Muhammad,
- Shangming Liu,
- Xiangfeng Chen,
- Jing Jiang,
- Jinsong Li,
- Wai-Yee Chan,
- Jinlong Ma,
- Gang Lu,
- Zi-Jiang Chen,
- Hongbin Liu
Affiliations
- Ke Xu
- Center for Reproductive Medicine, Shandong University, Jinan, China; Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China; Shandong Technology Innovation Center for Reproductive Health, Shanghai, China
- Xianwei Su
- CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China
- Kailun Fang
- ORCiD
- Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
- Yue Lv
- CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, China
- Tao Huang
- ORCiD
- Center for Reproductive Medicine, Shandong University, Jinan, China; Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China; Shandong Technology Innovation Center for Reproductive Health, Shanghai, China
- Mengjing Li
- Center for Reproductive Medicine, Shandong University, Jinan, China; Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China; Shandong Technology Innovation Center for Reproductive Health, Shanghai, China
- Ziqi Wang
- Center for Reproductive Medicine, Shandong University, Jinan, China; Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China; Shandong Technology Innovation Center for Reproductive Health, Shanghai, China
- Yingying Yin
- Center for Reproductive Medicine, Shandong University, Jinan, China; Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China; Shandong Technology Innovation Center for Reproductive Health, Shanghai, China
- Tahir Muhammad
- Center for Reproductive Medicine, Shandong University, Jinan, China; Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China; Shandong Technology Innovation Center for Reproductive Health, Shanghai, China
- Shangming Liu
- School of Basic Medical Sciences, Shandong University, Jinan, China
- Xiangfeng Chen
- Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China
- Jing Jiang
- Genome Tagging Project (GTP) Center, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China
- Jinsong Li
- ORCiD
- Genome Tagging Project (GTP) Center, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China
- Wai-Yee Chan
- Center for Reproductive Medicine, Shandong University, Jinan, China; CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China
- Jinlong Ma
- Center for Reproductive Medicine, Shandong University, Jinan, China; Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China; Shandong Technology Innovation Center for Reproductive Health, Shanghai, China
- Gang Lu
- Center for Reproductive Medicine, Shandong University, Jinan, China; CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China
- Zi-Jiang Chen
- ORCiD
- Center for Reproductive Medicine, Shandong University, Jinan, China; Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China; Shandong Technology Innovation Center for Reproductive Health, Shanghai, China; CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences, Shanghai, China
- Hongbin Liu
- ORCiD
- Center for Reproductive Medicine, Shandong University, Jinan, China; Key laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China; Shandong Technology Innovation Center for Reproductive Health, Shanghai, China; CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences, Shanghai, China
- DOI
- https://doi.org/10.7554/eLife.83129
- Journal volume & issue
-
Vol. 12
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 toward 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 knockout (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.
Keywords