Catsperς regulates the structural continuity of sperm ca2+ signaling domains and is required for normal fertility

Jean Ju Chung, Kiyoshi Miki, Doory Kim, Sang-Hee Shim, Huanan F. Shi, Jae Yeon Hwang, Xinjiang Cai, Yusuf Iseri, Xiaowei Zhuang, David E. Clapham

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38 Citations (Scopus)

Abstract

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 CatSperz is disrupted at ~0.8 mm 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 CatSpere is quadrilaterally arranged along the flagella, similar to the CatSper complex in mouse sperm. We speculate that the newly identified CatSperz subunit is a late evolutionary adaptation to maximize fertilization inside the mammalian female reproductive tract.

Original languageEnglish
Article numbere23082
JournaleLife
Volume6
DOIs
Publication statusPublished - 2017 Feb 23

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Chung, J. J., Miki, K., Kim, D., Shim, S-H., Shi, H. F., Hwang, J. Y., Cai, X., Iseri, Y., Zhuang, X., & Clapham, D. E. (2017). Catsperς regulates the structural continuity of sperm ca2+ signaling domains and is required for normal fertility. eLife, 6, [e23082]. https://doi.org/10.7554/eLife.23082