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TitleA red fluorescent genetically encoded biosensor for in vivo imaging of extracellular L-lactate dynamics.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 9531, Year 2025
Publish dateOct 29, 2025
AuthorsYuki Kamijo / Philipp Mächler / Natalie Ness / Cong Quang Vu / Tsukasa Kusakizako / Jamsad Mannuthodikayil / Zaneta Ku / Marc Boisvert / Ekaterina Grebenik / Ikumi Miyazaki / Rina Hashizume / Haruaki Sato / Rui Liu / Yukiko Hori / Taisuke Tomita / Tetsuro Katayama / Akihiro Furube / Gabriela Caraveo / Marie-Eve Paquet / Mikhail Drobizhev / Osamu Nureki / Satoshi Arai / Marco Brancaccio / Robert E Campbell / David Kleinfeld / Yusuke Nasu /
PubMed AbstractL-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 ...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.
External linksNat Commun / PubMed:41162396 / PubMed Central
MethodsEM (single particle)
Resolution2.7 Å
Structure data

60263

8zmz

EMDB-60263, PDB-8zmz:
Cryo-EM structure of R-eLACCO2 in the lactate-bound state
Method: EM (single particle) / Resolution: 2.7 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-2OP:
(2S)-2-HYDROXYPROPANOIC ACID

Source
  • Thermus thermophilus H8 (bacteria)
  • thermus thermophilus hb8 (bacteria)
  • discosoma sp. (sea anemone)
KeywordsFLUORESCENT PROTEIN

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