CatSper[zeta] regulates the structural continuity of sperm Ca.sup.2+ signaling domains and is required for normal fertility

• Published in: eLife 2017, 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: Report
• Language: English
• Subjects: Calcium (Nutrient); Cellular signal transduction; Fertility; Health aspects; Observations; Physiological aspects; Sperm
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.23082

We report that the Gm7068 (CatSpere) and Tex40 (CatSperz) genes encode novel subunits of a 9-subunit CatSper ion channel complex. Targeted disruption of CatSperz 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 CatSper[zeta] is disrupted at ~0.8 [mu]m 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 in vitro and efficiently migrating in vivo. Ejaculated CatSperz-null sperm cells retrieved from the mated female uterus partially rescue in vitro fertilization (IVF) that failed with epididymal spermatozoa alone. Human CatSper[epsilon] is quadrilaterally arranged along the flagella, similar to the CatSper complex in mouse sperm. We speculate that the newly identified CatSper[zeta] subunit is a late evolutionary adaptation to maximize fertilization inside the mammalian female reproductive tract.