Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging.
Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging.
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DOI：
10.1038/s41467-023-42230-5
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发表时间：
2023-10-27
影响因子：
16.6
通讯作者：
Campbell, Robert E.
中科院分区：
文献类型：
--
作者：
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.
L乳酸作为哺乳动物体内的一种关键代谢产物和信号分子，越来越受到重视。然而，由于L乳酸基因编码生物传感器的选择和性能有限，目前对L乳酸细胞内和细胞内动力学的研究受到阻碍。在这里，我们报告了一对光谱和功能正交的高性能基因编码生物传感器：绿色荧光细胞外L-乳酸生物传感器，命名为eLACCO2.1；红色荧光细胞内L-乳酸生物传感器，命名为R-iLACCO1。ELACCO2.1表现出良好的膜定位和强大的荧光响应。据我们所知，R-iLACCO1及其亲和变异体表现出比以往报道的任何细胞内L-乳酸生物传感器更强的荧光响应。我们通过eLACCO2.1和R-iLACCO1在培养细胞中的共表达，展示了L-乳酸动力学的光谱和空间多路成像，以及小鼠细胞外和细胞内L-乳酸动力学的体内成像。L-乳酸是哺乳动物体内的重要代谢产物和信号分子，但其体内研究方法一直受到限制。在这里，作者报告了一对改进的生物传感器-一个绿色和一个红色-用于在细胞内外可视化L-乳酸。
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. l-Lactate is increasingly recognized as a key metabolite and signalling molecule in mammals, but the methods to investigate it in vivo have been limited. Here, authors report a pair of improved biosensors—one green and one red—for visualizing l-lactate both inside and outside of cells.
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影响因子：
16.2
作者：
Choi HB;Gordon GR;Zhou N;Tai C;Rungta RL;Martinez J;Milner TA;Ryu JK;McLarnon JG;Tresguerres M;Levin LR;Buck J;MacVicar BA
通讯作者：
MacVicar BA
影响因子：
4.6
作者：
Harada K;Chihara T;Hayasaka Y;Mita M;Takizawa M;Ishida K;Arai M;Tsuno S;Matsumoto M;Ishihara T;Ueda H;Kitaguchi T;Tsuboi T
通讯作者：
Tsuboi T
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
29
作者：
Machler, Philipp;Wyss, Matthias T.;Weber, Bruno
通讯作者：
Weber, Bruno
超灵敏传感器揭示生理和疾病中乳酸代谢的时空景观
影响因子：
29
作者：
Li, Xi;Zhang, Yinan;Zhao, Yuzheng
通讯作者：
Zhao, Yuzheng