CCDC113 stabilizes sperm axoneme and head-tail coupling apparatus to ensure male fertility
Bingbing Wu,
Chenghong Long,
Yuzhuo Yang,
Zhe Zhang,
Shuang Ma,
Yanjie Ma,
Huafang Wei,
Jinghe Li,
Hui Jiang,
Wei Li,
Chao Liu
Affiliations
Bingbing Wu
Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Stem Cell and Regenerative Medicine Innovation Institute, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China
Chenghong Long
Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Yuzhuo Yang
Department of Urology, Department of Reproductive Medicine Center, Peking University Third Hospital, Beijing, China; Department of Urology, Peking University First Hospital Institute of Urology, Peking University, Beijing, China
Zhe Zhang
Department of Urology, Department of Reproductive Medicine Center, Peking University Third Hospital, Beijing, China; Department of Urology, Peking University First Hospital Institute of Urology, Peking University, Beijing, China
Shuang Ma
Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Stem Cell and Regenerative Medicine Innovation Institute, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China
Yanjie Ma
Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Stem Cell and Regenerative Medicine Innovation Institute, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China
Huafang Wei
Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Jinghe Li
Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Hui Jiang
Department of Urology, Department of Reproductive Medicine Center, Peking University Third Hospital, Beijing, China; Department of Urology, Peking University First Hospital Institute of Urology, Peking University, Beijing, China
Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Stem Cell and Regenerative Medicine Innovation Institute, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China
Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Stem Cell and Regenerative Medicine Innovation Institute, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China
The structural integrity of the sperm is crucial for male fertility, defects in sperm head-tail linkage and flagellar axoneme are associated with acephalic spermatozoa syndrome (ASS) and the multiple morphological abnormalities of the sperm flagella (MMAF). Notably, impaired head-tail coupling apparatus (HTCA) often accompanies defects in the flagellum structure, however, the molecular mechanisms underlying this phenomenon remain elusive. Here, we identified an evolutionarily conserved coiled-coil domain-containing (CCDC) protein, CCDC113, and found the disruption of CCDC113 produced spermatozoa with disorganized sperm flagella and HTCA, which caused male infertility. Further analysis revealed that CCDC113 could bind to CFAP57 and CFAP91, and function as an adaptor protein for the connection of radial spokes, nexin-dynein regulatory complex (N-DRC), and doublet microtubules (DMTs) in the sperm axoneme. Moreover, CCDC113 was identified as a structural component of HTCA, collaborating with SUN5 and CENTLEIN to connect sperm head to tail during spermiogenesis. Together, our studies reveal that CCDC113 serve as a critical hub for sperm axoneme and HTCA stabilization in mice, providing insights into the potential pathogenesis of infertility associated with human CCDC113 mutations.