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

Research output: Contribution to journalArticlepeer-review

105 Citations (Scopus)


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
Publication statusPublished - 2017 Feb 23

Bibliographical note

Funding Information:
We thank M. Sanguinetti for testing CatSper expression in Xenopus oocytes for ICatSper detection, P. DeCaen for help with sperm electrophysiology, and L. Ded for calculating rib length from the literature and critical reading of the manuscript-in-progress. This work was supported by Goodman-Gilman Yale Scholar Award 2015–08 (J-JC), HHMI (XZ), and HHMI (DEC).

Publisher Copyright:
© Chung et al.

ASJC Scopus subject areas

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


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