title: CatSperζ regulates the structural continuity of sperm Ca2+signaling domains and is required for normal fertility.
abstract: We report that theGm7068(CatSpere) andTex40(CatSperz) genes encode novel subunits of a 9-subunit CatSper ion channel complex. Targeted disruption ofCatSperzreduces 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 flowin vitroand efficiently migratingin vivo. EjaculatedCatSperz-null sperm cells retrieved from the mated female uterus partially rescuein vitrofertilization (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.
authors.affiliation: Howard Hughes Medical Institute, Boston Children's Hospital, Boston, United States.|Department of Neurobiology, Harvard Medical School, Boston, United States.|Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, United States.
authors.forename: Jean-Ju
authors.identifier: 0000-0001-8018-1355
authors.initials: JJ
authors.lastname: Chung
authors.affiliation: Howard Hughes Medical Institute, Boston Children's Hospital, Boston, United States.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Miki
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States.|Department of Physics, Harvard University, Cambridge, United States.
authors.forename: Doory
authors.initials: D
authors.lastname: Kim
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States.|Department of Physics, Harvard University, Cambridge, United States.
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Shim
authors.affiliation: Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, United States.
authors.forename: Huanan F
authors.identifier: 0000-0003-3710-5917
authors.initials: HF
authors.lastname: Shi
authors.affiliation: Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, United States.
authors.forename: Jae Yeon
authors.initials: JY
authors.lastname: Hwang
authors.affiliation: Department of Medicine, James J. Perters VA Bronx, Icahn School of Medicine at Mount Sinai, New York, United States.
authors.forename: Xinjiang
authors.identifier: 0000-0001-8933-7133
authors.initials: X
authors.lastname: Cai
authors.affiliation: Howard Hughes Medical Institute, Boston Children's Hospital, Boston, United States.
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Iseri
authors.affiliation: Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, Cambridge, United States.|Department of Physics, Harvard University, Cambridge, United States.
authors.forename: Xiaowei
authors.identifier: 0000-0002-6034-7853
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: Howard Hughes Medical Institute, Boston Children's Hospital, Boston, United States.|Department of Neurobiology, Harvard Medical School, Boston, United States.
authors.forename: David E
authors.identifier: 0000-0002-4459-9428
authors.initials: DE
authors.lastname: Clapham
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling; D002465:Cell Movement; D005298:Fertility; D055786:Gene Knockout Techniques; D008297:Male; D051379:Mice; D013094:Spermatozoa / Q000502:physiology*
chemical_list: D015220:Calcium Channels
keywords: Ca2+ channels; biophysics; cell biology; human; mammalian fertilization; mouse; rheotaxis; sperm motility; structural biology; super-resolution imaging