CatSperζ regulates the structural continuity of sperm Ca 2+ signaling domains and is required for normal fertility

We report that the ( ) and ( ) genes encode novel subunits of a 9-subunit CatSper ion channel complex. Targeted disruption of reduces CatSper current and sperm rheotactic efficiency in mice, resulting in severe male subfertility. Normally distributed in linear quadrilateral nanodomains along the fla...

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Bibliographic Details
Published in:eLife 2017-02, Vol.6
Main Authors: Chung, Jean-Ju, Miki, Kiyoshi, Kim, Doory, Shim, Sang-Hee, Shi, Huanan F, Hwang, Jae Yeon, Cai, Xinjiang, Iseri, Yusuf, Zhuang, Xiaowei, Clapham, David E
Format: Article
Language:English
Subjects:
Animals
Calcium Channels - genetics
Calcium Channels - metabolism
Calcium Signaling
Cell Movement
Fertility
Gene Knockout Techniques
Male
Mice
Spermatozoa - physiology
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Summary:We report that the ( ) and ( ) genes encode novel subunits of a 9-subunit CatSper ion channel complex. Targeted disruption of reduces CatSper current and sperm rheotactic efficiency in mice, resulting in severe male subfertility. Normally distributed in linear quadrilateral nanodomains along the flagellum, the complex lacking CatSperζ is disrupted at ~0.8 μm intervals along the flagellum. This disruption renders the proximal flagellum inflexible and alters the 3D flagellar envelope, thus preventing sperm from reorienting against fluid flow and efficiently migrating . Ejaculated -null sperm cells retrieved from the mated female uterus partially rescue fertilization (IVF) that failed with epididymal spermatozoa alone. Human CatSperε is quadrilaterally arranged along the flagella, similar to the CatSper complex in mouse sperm. We speculate that the newly identified CatSperζ subunit is a late evolutionary adaptation to maximize fertilization inside the mammalian female reproductive tract.
ISSN:2050-084X
DOI:10.7554/eLife.23082