biostudies-literatureChung JJYale School of MedicineHoward Hughes Medical Institutee23082https://www.ebi.ac.uk/biostudies/studies/S-EPMC5362262biostudies-literatureUnknown6We report that the <i>Gm7068</i> (<i>CatSpere</i>) and <i>Tex40</i> (<i>CatSperz</i>) genes encode novel subunits of a 9-subunit CatSper ion channel complex. Targeted disruption of <i>CatSperz</i> 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 <i>in vitro</i> and efficiently migrating <i>in vivo</i>. Ejaculated <i>CatSperz</i>-null sperm cells retrieved from the mated female uterus partially rescue <i>in vitro</i> fertilizaeLifeCatSperζ regulates the structural continuity of sperm Ca²⁺ signaling domains and is required for normal fertility.PMC5362262Goodman-Gilman Yale Scholar Award 2015-08Kim DClapham DEIseri YShi HFZhuang XHwang JYShim SHMiki KChung JJCai XfalseCatSperζ regulates the structural continuity of sperm Ca²⁺ signaling domains and is required for normal fertility.We report that the <i>Gm7068</i> (<i>CatSpere</i>) and <i>Tex40</i> (<i>CatSperz</i>) genes encode novel subunits of a 9-subunit CatSper ion channel complex. Targeted disruption of <i>CatSperz</i> 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 <i>in vitro</i> and efficiently migrating <i>in vivo</i>. Ejaculated <i>CatSperz</i>-null sperm cells retrieved from the mated female uterus partially rescue <i>in vitro</i> fertiliza2017-01-01T00:00:00Z2017 Feb2026-04-08T04:03:36.685Z2019-03-27T02:39:16ZS-EPMC53622622822624110.7554/eLife.23082