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Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging

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 no...

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Autores principales: Nasu, Yusuke, Aggarwal, Abhi, Le, Giang N. T., Vo, Camilla Trang, Kambe, Yuki, Wang, Xinxing, Beinlich, Felix R. M., Lee, Ashley Bomin, Ram, Tina R., Wang, Fangying, Gorzo, Kelsea A., Kamijo, Yuki, Boisvert, Marc, Nishinami, Suguru, Kawamura, Genki, Ozawa, Takeaki, Toda, Hirofumi, Gordon, Grant R., Ge, Shaoyu, Hirase, Hajime, Nedergaard, Maiken, Paquet, Marie-Eve, Drobizhev, Mikhail, Podgorski, Kaspar, Campbell, Robert E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10611801/
https://www.ncbi.nlm.nih.gov/pubmed/37891202
http://dx.doi.org/10.1038/s41467-023-42230-5
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author Nasu, Yusuke
Aggarwal, Abhi
Le, Giang N. T.
Vo, Camilla Trang
Kambe, Yuki
Wang, Xinxing
Beinlich, Felix R. M.
Lee, Ashley Bomin
Ram, Tina R.
Wang, Fangying
Gorzo, Kelsea A.
Kamijo, Yuki
Boisvert, Marc
Nishinami, Suguru
Kawamura, Genki
Ozawa, Takeaki
Toda, Hirofumi
Gordon, Grant R.
Ge, Shaoyu
Hirase, Hajime
Nedergaard, Maiken
Paquet, Marie-Eve
Drobizhev, Mikhail
Podgorski, Kaspar
Campbell, Robert E.
author_facet Nasu, Yusuke
Aggarwal, Abhi
Le, Giang N. T.
Vo, Camilla Trang
Kambe, Yuki
Wang, Xinxing
Beinlich, Felix R. M.
Lee, Ashley Bomin
Ram, Tina R.
Wang, Fangying
Gorzo, Kelsea A.
Kamijo, Yuki
Boisvert, Marc
Nishinami, Suguru
Kawamura, Genki
Ozawa, Takeaki
Toda, Hirofumi
Gordon, Grant R.
Ge, Shaoyu
Hirase, Hajime
Nedergaard, Maiken
Paquet, Marie-Eve
Drobizhev, Mikhail
Podgorski, Kaspar
Campbell, Robert E.
author_sort Nasu, Yusuke
collection PubMed
description 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.
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spelling pubmed-106118012023-10-29 Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging Nasu, Yusuke Aggarwal, Abhi Le, Giang N. T. Vo, Camilla Trang Kambe, Yuki Wang, Xinxing Beinlich, Felix R. M. Lee, Ashley Bomin Ram, Tina R. Wang, Fangying Gorzo, Kelsea A. Kamijo, Yuki Boisvert, Marc Nishinami, Suguru Kawamura, Genki Ozawa, Takeaki Toda, Hirofumi Gordon, Grant R. Ge, Shaoyu Hirase, Hajime Nedergaard, Maiken Paquet, Marie-Eve Drobizhev, Mikhail Podgorski, Kaspar Campbell, Robert E. Nat Commun Article 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. Nature Publishing Group UK 2023-10-27 /pmc/articles/PMC10611801/ /pubmed/37891202 http://dx.doi.org/10.1038/s41467-023-42230-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Nasu, Yusuke
Aggarwal, Abhi
Le, Giang N. T.
Vo, Camilla Trang
Kambe, Yuki
Wang, Xinxing
Beinlich, Felix R. M.
Lee, Ashley Bomin
Ram, Tina R.
Wang, Fangying
Gorzo, Kelsea A.
Kamijo, Yuki
Boisvert, Marc
Nishinami, Suguru
Kawamura, Genki
Ozawa, Takeaki
Toda, Hirofumi
Gordon, Grant R.
Ge, Shaoyu
Hirase, Hajime
Nedergaard, Maiken
Paquet, Marie-Eve
Drobizhev, Mikhail
Podgorski, Kaspar
Campbell, Robert E.
Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging
title Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging
title_full Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging
title_fullStr Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging
title_full_unstemmed Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging
title_short Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging
title_sort lactate biosensors for spectrally and spatially multiplexed fluorescence imaging
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10611801/
https://www.ncbi.nlm.nih.gov/pubmed/37891202
http://dx.doi.org/10.1038/s41467-023-42230-5
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