A red fluorescent genetically encoded biosensor for in vivo imaging of extracellular l-lactate dynamics

L-Lactate is increasingly recognized as an intercellular energy currency in mammals, but mysteries remain regarding the spatial and temporal dynamics of its release and uptake between cells via the extracellular environment. Here we introduce R-eLACCO2.1, a red fluorescent extracellular L-lactate biosensor that is superior to previously reported green fluorescent biosensors in in vivo sensitivity to increases in extracellular L-lactate and spectral orthogonality. R-eLACCO2.1 exhibits excellent fluorescence response in cultured cells, mouse brain slices, and live mice. R-eLACCO2.1 also serves as an effective fluorescence lifetime-based biosensor. Using R-eLACCO2.1, we monitor whisker stimulation and locomotion-induced changes in endogenous extracellular L-lactate in the somatosensory cortex of awake mice. To highlight the potential insights gained from in vivo measurements with R-eLACCO2.1, we perform dual-color imaging from the somatosensory cortex of actively locomoting mice. This enables us to simultaneously observe the neural activity, reported by a green fluorescent GCaMP calcium ion biosensor, and extracellular L-lactate. As the high-performance tool in the suite of extracellular L-lactate biosensors, R-eLACCO2.1 is ideally suited to delimit the emerging roles of L-lactate in mammalian metabolism.

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Publication Details

Journal
Nature Communications
Published
2025-10-29
DOI
https://doi.org/10.1038/s41467-025-64484-x
Citations
1
Primary Topic
Neuroscience and Neuropharmacology Research
Type
article
Field-Weighted Citation Impact
0.91

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article

A red fluorescent genetically encoded biosensor for in vivo imaging of extracellular l-lactate dynamics

Marco Brancaccio, Tsukasa Kusakizako, Osamu Nureki, David Kleinfeld et al.
1 citations
Nature Communications
Neuroscience and Neuropharmacology Research
0.91
article

A red fluorescent genetically encoded biosensor for in vivo imaging of extracellular l-lactate dynamics

Marco Brancaccio, Tsukasa Kusakizako, Osamu Nureki, David Kleinfeld, Ekaterina A. Grebenik, Natalie Ness, Akihiro Furube, Ikumi Miyazaki, Yukiko Hori, Cong Quang Vu, Yusuke Nasu, Zaneta Ku, Jamsad Mannuthodikayil, Rina Hashizume, Marie-Ève Paquet, Gabriela Caraveo, Yuki Kamijo, Marc Boisvert, Haruaki Sato, Philipp Mächler, Tetsuro Katayama, Robert E. Campbell, Mikhail Drobizhev, Satoshi Arai, Taisuke Tomita, Rui Liu
article en
1 citations

Abstract

L-Lactate is increasingly recognized as an intercellular energy currency in mammals, but mysteries remain regarding the spatial and temporal dynamics of its release and uptake between cells via the extracellular environment. Here we introduce R-eLACCO2.1, a red fluorescent extracellular L-lactate biosensor that is superior to previously reported green fluorescent biosensors in in vivo sensitivity to increases in extracellular L-lactate and spectral orthogonality. R-eLACCO2.1 exhibits excellent fluorescence response in cultured cells, mouse brain slices, and live mice. R-eLACCO2.1 also serves as an effective fluorescence lifetime-based biosensor. Using R-eLACCO2.1, we monitor whisker stimulation and locomotion-induced changes in endogenous extracellular L-lactate in the somatosensory cortex of awake mice. To highlight the potential insights gained from in vivo measurements with R-eLACCO2.1, we perform dual-color imaging from the somatosensory cortex of actively locomoting mice. This enables us to simultaneously observe the neural activity, reported by a green fluorescent GCaMP calcium ion biosensor, and extracellular L-lactate. As the high-performance tool in the suite of extracellular L-lactate biosensors, R-eLACCO2.1 is ideally suited to delimit the emerging roles of L-lactate in mammalian metabolism.

Nature CommunicationsVol. 16(1)
Kanazawa University (JP), Northwestern University (US), National Taiwan University (TW), Montana State University (US), University of California San Diego (US), Institute of Biological Chemistry, Academia Sinica (TW), Life Science Institute (JP), UK Dementia Research Institute (GB), Université Laval (CA), Imperial College London (GB), The University of Tokyo (JP), Tokushima University (JP)
Montana State University, Precise Measurement Technology Promotion Foundation, Kanazawa University, Imperial College London, Academia Sinica, Nakatani Foundation for Advancement of Measuring Technologies in Biomedical Engineering, UK Dementia Research Institute, National Institutes of Health, Medical Research Council, Japan Society for the Promotion of Science, Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Precursory Research for Embryonic Science and Technology
Openalex Percentile: Top 21%
Neuroscience and Neuropharmacology Research
0.91
DOIOpen Access PDFOpenAlex
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