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Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging

Author

Listed:
  • Yusuke Nasu

    (The University of Tokyo, Bunkyo-ku
    PRESTO, Japan Science and Technology Agency, Chiyoda-ku)

  • Abhi Aggarwal

    (Janelia Research Campus, Howard Hughes Medical Institute
    Allen Institute for Neural Dynamics)

  • Giang N. T. Le

    (The University of Tokyo, Bunkyo-ku
    University of Toronto)

  • Camilla Trang Vo

    (University of Copenhagen)

  • Yuki Kambe

    (Kagoshima University, Sakuragaoka)

  • Xinxing Wang

    (Stony Brook University)

  • Felix R. M. Beinlich

    (University of Copenhagen)

  • Ashley Bomin Lee

    (University of Copenhagen)

  • Tina R. Ram

    (University of Calgary)

  • Fangying Wang

    (University of Calgary)

  • Kelsea A. Gorzo

    (University of Calgary)

  • Yuki Kamijo

    (The University of Tokyo, Bunkyo-ku)

  • Marc Boisvert

    (CERVO Brain Research Centre
    Laval University)

  • Suguru Nishinami

    (University of Tsukuba, Tsukuba)

  • Genki Kawamura

    (The University of Tokyo, Bunkyo-ku)

  • Takeaki Ozawa

    (The University of Tokyo, Bunkyo-ku)

  • Hirofumi Toda

    (University of Tsukuba, Tsukuba)

  • Grant R. Gordon

    (University of Calgary)

  • Shaoyu Ge

    (Stony Brook University)

  • Hajime Hirase

    (University of Copenhagen
    University of Rochester Medical Center)

  • Maiken Nedergaard

    (University of Copenhagen
    University of Rochester Medical Center)

  • Marie-Eve Paquet

    (CERVO Brain Research Centre
    Laval University)

  • Mikhail Drobizhev

    (Montana State University)

  • Kaspar Podgorski

    (Janelia Research Campus, Howard Hughes Medical Institute
    Allen Institute for Neural Dynamics)

  • Robert E. Campbell

    (The University of Tokyo, Bunkyo-ku
    CERVO Brain Research Centre
    Laval University)

Abstract

l-Lactate is increasingly appreciated as a key metabolite and signaling molecule in mammals. However, investigations of the inter- and intra-cellular dynamics of l-lactate are currently hampered by the limited selection and performance of l-lactate-specific genetically encoded biosensors. Here we now report a spectrally and functionally orthogonal pair of high-performance genetically encoded biosensors: a green fluorescent extracellular l-lactate biosensor, designated eLACCO2.1, and a red fluorescent intracellular l-lactate biosensor, designated R-iLACCO1. eLACCO2.1 exhibits excellent membrane localization and robust fluorescence response. To the best of our knowledge, R-iLACCO1 and its affinity variants exhibit larger fluorescence responses than any previously reported intracellular l-lactate biosensor. We demonstrate spectrally and spatially multiplexed imaging of l-lactate dynamics by coexpression of eLACCO2.1 and R-iLACCO1 in cultured cells, and in vivo imaging of extracellular and intracellular l-lactate dynamics in mice.

Suggested Citation

  • Yusuke Nasu & Abhi Aggarwal & Giang N. T. Le & Camilla Trang Vo & Yuki Kambe & Xinxing Wang & Felix R. M. Beinlich & Ashley Bomin Lee & Tina R. Ram & Fangying Wang & Kelsea A. Gorzo & Yuki Kamijo & Ma, 2023. "Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42230-5
    DOI: 10.1038/s41467-023-42230-5
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    References listed on IDEAS

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    1. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
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