| First Author | Wang M | Year | 2023 |
| Journal | Natl Sci Rev | Volume | 10 |
| Issue | 9 | Pages | nwad181 |
| PubMed ID | 37601242 | Mgi Jnum | J:345163 |
| Mgi Id | MGI:7582036 | Doi | 10.1093/nsr/nwad181 |
| Citation | Wang M, et al. (2023) CCDC189 affects sperm flagellum formation by interacting with CABCOCO1. Natl Sci Rev 10(9):nwad181 |
| abstractText | Multiple morphological abnormalities of the sperm flagella (MMAF) are one of the major causes of male infertility and are characterized by multiple defects. In this study, we found that the coiled-coil domain-containing 189 (Ccdc189) gene was predominantly expressed in mouse testes and that inactivation of the Ccdc189 gene caused male infertility. Histological studies revealed that most sperm from Ccdc189-deficient mice carried coiled, curved or short flagella, which are typical MMAF phenotypes. Immunoelectron microscopy showed that the CCDC189 protein was located at the radial spoke of the first peripheral microtubule doublet in the sperm axoneme. A CCDC189-interacting protein, CABCOCO1 (ciliary-associated calcium-binding coiled-coil protein 1), was discovered via co-immunoprecipitation and mass spectrometry, and inactivation of Cabcoco1 caused malformation of sperm flagella, which was consistent with findings obtained with Ccdc189-deficient mice. Further studies revealed that inactivation of CCDC189 caused downregulation of CABCOCO1 protein expression and that both CCDC189 and CABCOCO1 interacted with the radial-spoke-specific protein RSPH1 and intraflagellar transport proteins. This study demonstrated that Ccdc189 is a radial-spoke-associated protein and is involved in sperm flagellum formation through its interactions with CABCOCO1 and intraflagellar transport proteins. |
