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Engineering of a bona fide light-operated calcium channel

Author

Listed:
  • Lian He

    (Texas A&M University)

  • Liuqing Wang

    (College of Life Sciences, Beijing Normal University)

  • Hongxiang Zeng

    (Texas A&M University)

  • Peng Tan

    (Texas A&M University)

  • Guolin Ma

    (Texas A&M University)

  • Sisi Zheng

    (College of Life Sciences, Beijing Normal University)

  • Yaxin Li

    (College of Life Sciences, Beijing Normal University)

  • Lin Sun

    (College of Life Sciences, Beijing Normal University)

  • Fei Dou

    (College of Life Sciences, Beijing Normal University)

  • Stefan Siwko

    (Texas A&M University)

  • Yun Huang

    (Texas A&M University
    College of Medicine, Texas A&M University)

  • Youjun Wang

    (College of Life Sciences, Beijing Normal University)

  • Yubin Zhou

    (Texas A&M University
    College of Medicine, Texas A&M University)

Abstract

The current optogenetic toolkit lacks a robust single-component Ca2+-selective ion channel tailored for remote control of Ca2+ signaling in mammals. Existing tools are either derived from engineered channelrhodopsin variants without strict Ca2+ selectivity or based on the stromal interaction molecule 1 (STIM1) that might crosstalk with other targets. Here, we describe the design of a light-operated Ca2+ channel (designated LOCa) by inserting a plant-derived photosensory module into the intracellular loop of an engineered ORAI1 channel. LOCa displays biophysical features reminiscent of the ORAI1 channel, which enables precise optical control over Ca2+ signals and hallmark Ca2+-dependent physiological responses. Furthermore, we demonstrate the use of LOCa to modulate aberrant hematopoietic stem cell self-renewal, transcriptional programming, cell suicide, as well as neurodegeneration in a Drosophila model of amyloidosis.

Suggested Citation

  • Lian He & Liuqing Wang & Hongxiang Zeng & Peng Tan & Guolin Ma & Sisi Zheng & Yaxin Li & Lin Sun & Fei Dou & Stefan Siwko & Yun Huang & Youjun Wang & Yubin Zhou, 2021. "Engineering of a bona fide light-operated calcium channel," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20425-4
    DOI: 10.1038/s41467-020-20425-4
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