부산대학교 도서관

The molecular mechanism underlying asymmetric axonemal complexes in sperm flagella is still largely unknown. Here, we showed that the knockout of the coiled-coil domain-containing 176 (CCDC176) in mice led to male infertility due to decreased sperm motility. Ccdc176 knockout specifically destabilized microtubule doublets (MTDs) 1 and 9 during sperm maturation in the corpus epididymis. Single-sperm immunofluorescence showed that most CCDC176 was distributed along the axoneme, and further super-resolution imaging revealed that CCDC176 is asymmetrically localized in the sperm axoneme. CCDC176 could cooperate with microtubule and radial spoke proteins to stabilize MTDs 1 and 9, and its knockout results in the destabilization of some proteins in sperm flagella. Furthermore, as predicted by the sperm multibody dynamics (MBD) model, we found that MTDs 1 and 9 jutted out from the sperm flagellum annulus region in Ccdc176 −/− spermatozoa, and these flagellar defects alter sperm flagellar beat patterns and swimming paths, potentially owing to the reduction and disequilibration of bending torque on the central pair. These results demonstrate that CCDC176 specifically stabilizes MTDs 1 and 9 in the sperm flagellum to ensure proper sperm movement for fertilization. • CCDC176 is asymmetrically localized in the sperm axoneme • Ccdc176 knockout results in MTDs 1 and 9 jutting out from the sperm flagellum • CCDC176 specifically stabilizes MTDs 1 and 9 by interacting with CCDC81 • MTDs 1 and 9 jutting out alter sperm flagellar beat patterns and swimming paths Liu et al. show that CCDC176 is asymmetrically localized in the sperm axoneme and simultaneously interacts with microtubule and radial spoke proteins. The knockout of this gene results in MTDs 1 and 9 jutting out from the sperm flagellum annulus region, alters sperm flagellar beat patterns and swimming paths, and finally leads to male infertility. [ABSTRACT FROM AUTHOR]