CatSperζ regulates the structural continuity of sperm Ca2+ signaling domains and is required for normal fertility
- Yale School of Medicine, United States
- Howard Hughes Medical Institute, Boston Children's Hospital, United States
- Howard Hughes Medical Institute, Harvard University, United States
- Ichan School of Medicine at Mount Sinai, United States
Abstract
We report that the Gm7068 (CatSperε) and Tex40 (CatSperζ) genes encode novel subunits of a 9-subunit CatSper ion channel complex. Targeted disruption of CatSperζ 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 in vitro and efficiently migrating in vivo. Ejaculated CatSperζ-null sperm cells retrieved from the mated female uterus partially rescue in vitro 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.
Article and author information
Author details
Funding
Howard Hughes Medical Institute
- Xiaowei Zhuang
- David E Clapham
Yale School of Medicine (Goodman-Gilman Yale Scholar Award 2015-08)
- Jean-Ju Chung
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All the mice were treated in accordance with guidelines approved by the Boston Children's Hospital (13-01-2341R) and Yale (2015-20079) Animal Care and Use Committees (IACUC).
Reviewing Editor
- Kenton J Swartz, National Institutes of Health, United States
Publication history
- Received: November 8, 2016
- Accepted: February 20, 2017
- Accepted Manuscript published: February 22, 2017 (version 1)
- Accepted Manuscript updated: February 23, 2017 (version 2)
- Version of Record published: March 22, 2017 (version 3)
Copyright
© 2017, Chung et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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CatSperζ 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
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