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CatSper and its CaM‐like Ca 2+ sensor EFCAB9 are necessary for the path chirality of sperm
Author(s) -
Wiesehöfer Caroline,
Wiesehöfer Marc,
Dankert Jaroslaw Thomas,
Chung JeanJu,
Ostau Nicola Edith,
Singer Bernhard Bonaventura,
Wennemuth Gunther
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202101656rr
Subject(s) - hyperactivation , sperm , zona pellucida , capacitation , microbiology and biotechnology , sperm motility , acrosome reaction , chemistry , chirality (physics) , motility , biology , physics , genetics , oocyte , embryo , chiral symmetry breaking , quantum mechanics , quark , nambu–jona lasinio model
Successful fertilization depends on sperm motility adaptation. Ejaculated and activated sperm beat symmetrically in high frequency, move linearly, and swim with clockwise chirality. After capacitation, sperm beat asymmetrically with lower amplitude and a high lateral head excursion. This motility change called hyperactivation requires CatSper activation and an increase in intracellular Ca 2+ . However, whether CatSper‐mediated Ca 2+ influx participates in controlling the swim path chirality is unknown. In this study, we show that the clockwise path chirality is preserved in mouse sperm regardless of capacitation state but is lost in the sperm either lacking the entire CatSper channel or its Ca 2+ sensor EFCAB9. Pharmacological inhibition of CatSper with either mibefradil or NNC 55‐0396 leads to the same loss in swim path chirality. Exposure of sperm to the recombinant N‐terminal part of the zona pellucida protein 2 randomizes chirality in capacitated cells, but not in non‐capacitated ones. We conclude that Ca 2+ sensitive regulation of CatSper activity orchestrates clockwise swim path chirality of sperm and any substantial change, such as the physiological stimulus of zona pellucida glycoproteins, results in a loss of chirality.