Nasu, Y., Aggarwal, A., Le, G.N.T., Vo, C.T., Kambe, Y., Wang, X., Beinlich, F.R.M., Lee, A.B., Ram, T.R., Wang, F., Gorzo, K.A., Kamijo, Y., Boisvert, M., Nishinami, S., Kawamura, G., Ozawa, T., Toda, H., Gordon, G.R., Ge, S., Hirase, H., Nedergaard, M., Paquet, M.E., Drobizhev, M., Podgorski, K., Campbell, R.E. (2023). Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging.  Nat. Commun. 14(1): 6598.

FBrf0261728

Research paper

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.

PMC10611801 (PMC) (EuropePMC)