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Highly dynamic and sensitive NEMOer calcium indicators for imaging ER calcium signals in excitable cells

Author

Listed:
  • Wenjia Gu

    (Beijing Normal University)

  • Jia-Hui Chen

    (Anhui Medical University)

  • Yiyin Zhang

    (Peking University)

  • Zhirong Wang

    (Chinese Academy of Sciences)

  • Jia Li

    (Beijing Normal University)

  • Sijia Wang

    (Chinese Academy of Sciences)

  • Hanhan Zhang

    (Beijing Normal University)

  • Amin Jiang

    (Chinese Academy of Sciences)

  • Ziyi Zhong

    (Beijing Normal University)

  • Jiaxuan Zhang

    (Beijing Normal University)

  • Ze Xu

    (Peking University)

  • Panpan Liu

    (Beijing Normal University)

  • Chao Xi

    (Beijing Normal University)

  • Tingting Hou

    (Peking University)

  • Donald L. Gill

    (Pennsylvania State University College of Medicine)

  • Dong Li

    (Chinese Academy of Sciences)

  • Yu Mu

    (Chinese Academy of Sciences)

  • Shi-Qiang Wang

    (Peking University)

  • Ai-Hui Tang

    (Hefei Comprehensive National Science Center
    University of Science and Technology of China)

  • Youjun Wang

    (Beijing Normal University
    Beijing Normal University)

Abstract

The Endoplasmic/sarcoplasmic reticulum (ER/SR) is central to calcium (Ca2+) signaling, yet current genetically encoded Ca2+ indicators (GECIs) cannot detect elementary Ca2+ release events from ER/SR, particularly in muscle cells. Here, we report NEMOer, a set of organellar GECIs, to efficiently capture ER Ca2+ dynamics with increased sensitivity and responsiveness. NEMOer indicators exhibit dynamic ranges an order of magnitude larger than G-CEPIA1er, enabling 2.7-fold more sensitive detection of Ca2+ transients in both non-excitable and excitable cells. The ratiometric version further allows super-resolution monitoring of local ER Ca2+ homeostasis and dynamics. Notably, NEMOer-f enabled the inaugural detection of Ca2+ blinks, elementary Ca2+ releasing signals from the SR of cardiomyocytes, as well as in vivo spontaneous SR Ca2+ releases in zebrafish. In summary, the highly dynamic NEMOer sensors expand the repertoire of organellar Ca2+ sensors that allow real-time monitoring of intricate Ca2+ dynamics and homeostasis in live cells with high spatiotemporal resolution.

Suggested Citation

  • Wenjia Gu & Jia-Hui Chen & Yiyin Zhang & Zhirong Wang & Jia Li & Sijia Wang & Hanhan Zhang & Amin Jiang & Ziyi Zhong & Jiaxuan Zhang & Ze Xu & Panpan Liu & Chao Xi & Tingting Hou & Donald L. Gill & Do, 2025. "Highly dynamic and sensitive NEMOer calcium indicators for imaging ER calcium signals in excitable cells," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58705-6
    DOI: 10.1038/s41467-025-58705-6
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