Calcium-independent biosensors for multiplexed in vivo imaging of extracellular lactate dynamics
- 1Academia Sinica
Abstract
Extracellular L-lactate reports cellular metabolism, but resolving its dynamics alongside intracellular metabolism and neuronal activity remains challenging. Here we develop eLACCO3 and R-eLACCO3, green and red cell-surface lactate biosensors with Ca2+-independent responses and faster response and recovery kinetics in cultured cells. Selected variants provide larger fluorescence responses than their predecessors in brain cells, slices, and living mice and improve detection of glucose-evoked extracellular lactate oscillations. Combining R-eLACCO3 with GCaMP6f enabled imaging of extracellular L-lactate simultaneously with odor-evoked activity in anesthetized mice and cortical activity in awake mice. These biosensors enable multiplexed measurements of extracellular lactate dynamics in relation to intracellular metabolism and neuronal activity.
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BibTeX
@misc{liu2026calciumindependent,
title = {{Calcium-independent biosensors for multiplexed in vivo imaging of extracellular lactate dynamics}},
author = {J.-J. Liu and H. Mizuno and E. Than-Trong and P. Machler and H. Kubotera and T. Barbay and C.-Y. Wang and Q.-L. To and Y. Kamijo and T. Nishimura and M. Boisvert and M.-E. Paquet and M. Drobizhev and S. J. Cragg and J. Nagai and D. Kleinfeld and S. Charpak and Y. NASU},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.02.756141},
url = {https://www.biorxiv.org/content/10.64898/2026.10.02.756141v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Calcium-independent biosensors for multiplexed in vivo imaging of extracellular lactate dynamics
AU - J.-J. Liu
AU - H. Mizuno
AU - E. Than-Trong
AU - P. Machler
AU - H. Kubotera
AU - T. Barbay
AU - C.-Y. Wang
AU - Q.-L. To
AU - Y. Kamijo
AU - T. Nishimura
AU - M. Boisvert
AU - M.-E. Paquet
AU - M. Drobizhev
AU - S. J. Cragg
AU - J. Nagai
AU - D. Kleinfeld
AU - S. Charpak
AU - Y. NASU
PY - 2026
DA - 2026/10/02
PB - bioRxiv
DO - 10.64898/2026.10.02.756141
UR - https://www.biorxiv.org/content/10.64898/2026.10.02.756141v1
AB - Extracellular L-lactate reports cellular metabolism, but resolving its dynamics alongside intracellular metabolism and neuronal activity remains challenging. Here we develop eLACCO3 and R-eLACCO3, green and red cell-surface lactate biosensors with Ca2+-independent responses and faster response and recovery kinetics in cultured cells. Selected variants provide larger fluorescence responses than their predecessors in brain cells, slices, and living mice and improve detection of glucose-evoked extracellular lactate oscillations. Combining R-eLACCO3 with GCaMP6f enabled imaging of extracellular L-lactate simultaneously with odor-evoked activity in anesthetized mice and cortical activity in awake mice. These biosensors enable multiplexed measurements of extracellular lactate dynamics in relation to intracellular metabolism and neuronal activity.
ER -