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CCDC146 is required for sperm flagellum biogenesis and male fertility in mice.
Ma, Yanjie; Wu, Bingbing; Chen, Yinghong; Ma, Shuang; Wang, Liying; Han, Tingting; Lin, Xiaolei; Yang, Fulin; Liu, Chao; Zhao, Jianguo; Li, Wei.
Afiliação
  • Ma Y; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Stem Cell and Regenerative Medicine Innovation Institute, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing, 100101, China.
  • Wu B; Guangzhou Women and Children's Medical Center, Guangzhou Medical University, No. 9 Jinsui Road, Tianhe District, Guangzhou, 510623, China.
  • Chen Y; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Ma S; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Stem Cell and Regenerative Medicine Innovation Institute, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing, 100101, China.
  • Wang L; Guangzhou Women and Children's Medical Center, Guangzhou Medical University, No. 9 Jinsui Road, Tianhe District, Guangzhou, 510623, China.
  • Han T; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Lin X; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Stem Cell and Regenerative Medicine Innovation Institute, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing, 100101, China.
  • Yang F; Guangzhou Women and Children's Medical Center, Guangzhou Medical University, No. 9 Jinsui Road, Tianhe District, Guangzhou, 510623, China.
  • Liu C; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Zhao J; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Stem Cell and Regenerative Medicine Innovation Institute, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing, 100101, China.
  • Li W; Guangzhou Women and Children's Medical Center, Guangzhou Medical University, No. 9 Jinsui Road, Tianhe District, Guangzhou, 510623, China.
Cell Mol Life Sci ; 81(1): 1, 2023 Dec 01.
Article em En | MEDLINE | ID: mdl-38038747
Multiple morphological abnormalities of the flagella (MMAF) is a severe disease of male infertility, while the pathogenetic mechanisms of MMAF are still incompletely understood. Previously, we found that the deficiency of Ccdc38 might be associated with MMAF. To understand the underlying mechanism of this disease, we identified the potential partner of this protein and found that the coiled-coil domain containing 146 (CCDC146) can interact with CCDC38. It is predominantly expressed in the testes, and the knockout of this gene resulted in complete infertility in male mice but not in females. The knockout of Ccdc146 impaired spermiogenesis, mainly due to flagellum and manchette organization defects, finally led to MMAF-like phenotype. Furthermore, we demonstrated that CCDC146 could interact with both CCDC38 and CCDC42. It also interacts with intraflagellar transport (IFT) complexes IFT88 and IFT20. The knockout of this gene led to the decrease of ODF2, IFT88, and IFT20 protein levels, but did not affect CCDC38, CCDC42, or ODF1 expression. Additionally, we predicted and validated the detailed interactions between CCDC146 and CCDC38 or CCDC42, and built the interaction models at the atomic level. Our results suggest that the testis predominantly expressed gene Ccdc146 is essential for sperm flagellum biogenesis and male fertility, and its mutations might be associated with MMAF in some patients.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cauda do Espermatozoide / Infertilidade Masculina / Proteínas Associadas aos Microtúbulos Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cauda do Espermatozoide / Infertilidade Masculina / Proteínas Associadas aos Microtúbulos Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article