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- Title
3D structure and in situ arrangements of CatSper channel in the sperm flagellum.
- Authors
Zhao, Yanhe; Wang, Huafeng; Wiesehoefer, Caroline; Shah, Naman B.; Reetz, Evan; Hwang, Jae Yeon; Huang, Xiaofang; Wang, Tse-en; Lishko, Polina V.; Davies, Karen M.; Wennemuth, Gunther; Nicastro, Daniela; Chung, Jean-Ju
- Abstract
The sperm calcium channel CatSper plays a central role in successful fertilization as a primary Ca2+ gateway. Here, we applied cryo-electron tomography to visualize the higher-order organization of the native CatSper complex in intact mammalian sperm. The repeating CatSper units form long zigzag-rows along mouse and human sperm flagella. Above each tetrameric channel pore, most of the extracellular domains form a canopy that interconnects to a zigzag-shaped roof. Murine CatSper contains an additional wing-structure connected to the tetrameric channel. The intracellular domains link two neighboring channels to a diagonal array, suggesting a dimer formation. Fitting of an atomic model of isolated monomeric CatSper to the in situ map reveals supramolecular interactions and assembly of the CatSper complex. Loss of EFCAB9-CATSPERζ alters the architecture and interactions of the channels, resulting in fragmentation and misalignment of the zigzag-rows and disruption of flagellar movement in Efcab9−/− sperm. This work offers unique insights into the structural basis for understanding CatSper regulation of sperm motility. Sperm motility and male fertility requires function of the CatSper calcium channels. Here, using cryo-electron tomography, authors visualize the native in-cell 3D structure and higher-order organization of the CatSper as long zigzag rows along the sperm tail.
- Subjects
FLAGELLA (Microbiology); CALCIUM channels; SPERM motility; ATOMIC models; FERTILITY
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-31050-8