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3D structure and in situ arrangements of CatSper channel in the sperm flagellum

Author

Listed:
  • Yanhe Zhao

    (University of Texas Southwestern Medical Center)

  • Huafeng Wang

    (Yale School of Medicine)

  • Caroline Wiesehoefer

    (University of Duisburg-Essen, Medical Faculty)

  • Naman B. Shah

    (University of California
    Lawrence Berkeley National Laboratory)

  • Evan Reetz

    (University of Texas Southwestern Medical Center)

  • Jae Yeon Hwang

    (Yale School of Medicine)

  • Xiaofang Huang

    (Yale School of Medicine)

  • Tse-en Wang

    (Yale School of Medicine)

  • Polina V. Lishko

    (University of California
    Buck Institute for Research on Aging)

  • Karen M. Davies

    (University of California
    Lawrence Berkeley National Laboratory)

  • Gunther Wennemuth

    (University of Duisburg-Essen, Medical Faculty)

  • Daniela Nicastro

    (University of Texas Southwestern Medical Center)

  • Jean-Ju Chung

    (Yale School of Medicine
    Yale School of Medicine)

Abstract

The sperm calcium channel CatSper plays a central role in successful fertilization as a primary Ca2+ gateway. Here, we applied cryo-electron tomography to visualize the higher-order organization of the native CatSper complex in intact mammalian sperm. The repeating CatSper units form long zigzag-rows along mouse and human sperm flagella. Above each tetrameric channel pore, most of the extracellular domains form a canopy that interconnects to a zigzag-shaped roof. Murine CatSper contains an additional wing-structure connected to the tetrameric channel. The intracellular domains link two neighboring channels to a diagonal array, suggesting a dimer formation. Fitting of an atomic model of isolated monomeric CatSper to the in situ map reveals supramolecular interactions and assembly of the CatSper complex. Loss of EFCAB9-CATSPERζ alters the architecture and interactions of the channels, resulting in fragmentation and misalignment of the zigzag-rows and disruption of flagellar movement in Efcab9−/− sperm. This work offers unique insights into the structural basis for understanding CatSper regulation of sperm motility.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31050-8
    DOI: 10.1038/s41467-022-31050-8
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    References listed on IDEAS

    as
    1. 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.
    2. Dejian Ren & Betsy Navarro & Gloria Perez & Alexander C. Jackson & Shyuefang Hsu & Qing Shi & Jonathan L. Tilly & David E. Clapham, 2001. "A sperm ion channel required for sperm motility and male fertility," Nature, Nature, vol. 413(6856), pages 603-609, October.
    3. Shiyi Lin & Meng Ke & Yuqi Zhang & Zhen Yan & Jianping Wu, 2021. "Structure of a mammalian sperm cation channel complex," Nature, Nature, vol. 595(7869), pages 746-750, July.
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    Cited by:

    1. Elena Grahn & Svenja V. Kaufmann & Malika Askarova & Momchil Ninov & Luisa M. Welp & Thomas K. Berger & Henning Urlaub & U.Benjamin Kaupp, 2023. "Control of intracellular pH and bicarbonate by CO2 diffusion into human sperm," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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