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A novel gene required for male fertility and functional CATSPER channel formation in spermatozoa

Author

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  • Jean-Ju Chung

    (Howard Hughes Medical Institute, Manton Center for Orphan Disease, Children's Hospital
    Harvard Medical School)

  • Betsy Navarro

    (Howard Hughes Medical Institute, Manton Center for Orphan Disease, Children's Hospital
    Harvard Medical School)

  • Grigory Krapivinsky

    (Howard Hughes Medical Institute, Manton Center for Orphan Disease, Children's Hospital
    Harvard Medical School)

  • Luba Krapivinsky

    (Howard Hughes Medical Institute, Manton Center for Orphan Disease, Children's Hospital
    Harvard Medical School)

  • David E. Clapham

    (Howard Hughes Medical Institute, Manton Center for Orphan Disease, Children's Hospital
    Harvard Medical School)

Abstract

Calcium signalling is critical for successful fertilization. In spermatozoa, capacitation, hyperactivation of motility and the acrosome reaction are all mediated by increases in intracellular Ca2+. Cation channels of sperm proteins (CATSPERS1–4) form an alkalinization-activated Ca2+-selective channel required for the hyperactivated motility of spermatozoa and male fertility. Each of the CatSper1–4 genes encodes a subunit of a tetramer surrounding a Ca2+-selective pore, in analogy with other six-transmembrane ion channel α subunits. In addition to the pore-forming proteins, the sperm Ca2+ channel contains auxiliary subunits, CATSPERβ and CATSPERγ. Here, we identify the Tmem146 gene product as a novel subunit, CATSPERδ, required for CATSPER channel function. We find that mice lacking the sperm tail-specific CATSPERδ are infertile and their spermatozoa lack both Ca2+ current and hyperactivated motility. We show that CATSPERδ is an essential element of the CATSPER channel complex and propose that CATSPERδ is required for proper CATSPER channel assembly and/or transport.

Suggested Citation

  • Jean-Ju Chung & Betsy Navarro & Grigory Krapivinsky & Luba Krapivinsky & David E. Clapham, 2011. "A novel gene required for male fertility and functional CATSPER channel formation in spermatozoa," Nature Communications, Nature, vol. 2(1), pages 1-12, September.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1153
    DOI: 10.1038/ncomms1153
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    Cited by:

    1. Yanhe Zhao & Huafeng Wang & Caroline Wiesehoefer & Naman B. Shah & Evan Reetz & Jae Yeon Hwang & Xiaofang Huang & Tse-en Wang & Polina V. Lishko & Karen M. Davies & Gunther Wennemuth & Daniela Nicastr, 2022. "3D structure and in situ arrangements of CatSper channel in the sperm flagellum," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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