iScience (Apr 2024)
The deubiquitinase cofactor UAF1 interacts with USP1 and plays an essential role in spermiogenesis
- Ziqi Wang,
- Tongtong Li,
- Dongkai Liu,
- Mengjing Li,
- Shangming Liu,
- Xiaochen Yu,
- Hanzhen Li,
- Hui Song,
- Wei Zhao,
- Zhaojian Liu,
- Xiangfeng Chen,
- Gang Lu,
- Zi-Jiang Chen,
- Tao Huang,
- Hongbin Liu
Affiliations
- Ziqi Wang
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Jinan, Shandong 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong 250012, China
- Tongtong Li
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China
- Dongkai Liu
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Jinan, Shandong 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong 250012, China
- Mengjing Li
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Jinan, Shandong 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong 250012, China
- Shangming Liu
- School of Basic Medical Sciences, Shandong University, Jinan 250012, China
- Xiaochen Yu
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Jinan, Shandong 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong 250012, China
- Hanzhen Li
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China
- Hui Song
- Department of Immunology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
- Wei Zhao
- Department of Immunology, Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
- Zhaojian Liu
- Advanced Medical Research Institute, Shandong University, Jinan, China
- Xiangfeng Chen
- Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China
- Gang Lu
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China; CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, the Chinese University of Hong Kong, Hong Kong, China
- Zi-Jiang Chen
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Jinan, Shandong 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong 250012, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China; CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, the Chinese University of Hong Kong, Hong Kong, China; Corresponding author
- Tao Huang
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Jinan, Shandong 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong 250012, China; CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, the Chinese University of Hong Kong, Hong Kong, China; Corresponding author
- Hongbin Liu
- Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China; Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Jinan, Shandong 250012, China; Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong 250012, China; CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, the Chinese University of Hong Kong, Hong Kong, China; Corresponding author
- Journal volume & issue
-
Vol. 27,
no. 4
p. 109456
Abstract
Summary: Spermiogenesis defines the final phase of male germ cell differentiation. While multiple deubiquitinating enzymes have been linked to spermiogenesis, the impacts of deubiquitination on spermiogenesis remain poorly characterized. Here, we investigated the function of UAF1 in mouse spermiogenesis. We selectively deleted Uaf1 in premeiotic germ cells using the Stra8-Cre knock-in mouse strain (Uaf1 sKO), and found that Uaf1 is essential for spermiogenesis and male fertility. Further, UAF1 interacts and colocalizes with USP1 in the testes. Conditional knockout of Uaf1 in testes results in disturbed protein levels and localization of USP1, suggesting that UAF1 regulates spermiogenesis through the function of the deubiquitinating enzyme USP1. Using tandem mass tag-based proteomics, we identified that conditional knockout of Uaf1 in the testes results in reduced levels of proteins that are essential for spermiogenesis. Thus, we conclude that the UAF1/USP1 deubiquitinase complex is essential for normal spermiogenesis by regulating the levels of spermiogenesis-related proteins.
