Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 4, Pages 1219-1223Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0610286104
Keywords
calcium; contraception; flagella
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Funding
- NHLBI NIH HHS [T32 HL007572] Funding Source: Medline
- NICHD NIH HHS [R01 HD036022, HD045339, HD36022, R01 HD045339] Funding Source: Medline
- PHS HHS [U01 45857] Funding Source: Medline
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Mammalian spermatozoa become motile at ejaculation, but before they can fertilize the egg, they must acquire more thrust to penetrate the cumulus and zona pellucida. The forceful asymmetric motion of hyperactivated spermatozoa requires Ca2+ entry into the sperm tail by an alkalinization-activated voltage-sensitive Ca2+-selective current (I-CatSper). Hyperactivation requires CatSper1 and CatSper2 putative ion channel genes, but the function of two other related genes (CatSper3 and CatSper4) is not known. Here we show that targeted disruption of murine CatSper3 or CatSper4 also abrogated I-CatSper, sperm cell hyperactivated motility and male fertility but did not affect spermatogenesis or initial motility. Direct protein interactions among CatSpers, the sperm specificity of these proteins, and loss of I-CatSper in each of the four CatSper(-/-) mice indicate that CatSpers are highly specialized flagellar proteins.
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