Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging
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Published:2023-10-27
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Nasu YusukeORCID, Aggarwal AbhiORCID, Le Giang N. T.ORCID, Vo Camilla Trang, Kambe YukiORCID, Wang Xinxing, Beinlich Felix R. M.ORCID, Lee Ashley Bomin, Ram Tina R., Wang Fangying, Gorzo Kelsea A., Kamijo Yuki, Boisvert Marc, Nishinami Suguru, Kawamura Genki, Ozawa TakeakiORCID, Toda Hirofumi, Gordon Grant R.ORCID, Ge ShaoyuORCID, Hirase HajimeORCID, Nedergaard MaikenORCID, Paquet Marie-EveORCID, Drobizhev MikhailORCID, Podgorski KasparORCID, Campbell Robert E.ORCID
Abstract
Abstractl-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.
Funder
MEXT | Japan Society for the Promotion of Science MEXT | JST | Precursory Research for Embryonic Science and Technology
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference51 articles.
1. Rabinowitz, J. D. & Enerbäck, S. Lactate: the ugly duckling of energy metabolism. Nat Metab 2, 566–571 (2020). 2. Magistretti, P. J. & Allaman, I. Lactate in the brain: from metabolic end-product to signalling molecule. Nat. Rev. Neurosci. 19, 235–249 (2018). 3. Low, V., Li, Z. & Blenis, J. Metabolite activation of tumorigenic signaling pathways in the tumor microenvironment. Sci. Signal. 15, eabj4220 (2022). 4. Chadaideh, K. S. & Carmody, R. N. Host-microbial interactions in the metabolism of different dietary fats. Cell Metab. 33, 857–872 (2021). 5. Kao, K.-C., Vilbois, S., Tsai, C.-H. & Ho, P.-C. Metabolic communication in the tumour-immune microenvironment. Nat. Cell Biol. 24, 1574–1583 (2022).
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