An improved monomeric infrared fluorescent protein for neuronal and tumour brain imaging

Dan Yu, William Clay Gustafson, Chun Han, Céline Lafaye, Marjolaine Noirclerc-Savoye, Woo-Ping Ge, Desiree A. Thayer, Hai Huang, Thomas B. Kornberg, Antoine Royant, Lily Yeh Jan, Yuh Nung Jan, William A. Weiss and Xiaokun Shu ()
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Dan Yu: University of California
William Clay Gustafson: Helen Diller Family Comprehensive Cancer Center, University of California
Chun Han: Cardiovascular Research Institute, University of California
Céline Lafaye: Université Grenoble Alpes, Institut de Biologie Structurale (IBS)
Marjolaine Noirclerc-Savoye: Université Grenoble Alpes, Institut de Biologie Structurale (IBS)
Woo-Ping Ge: Cardiovascular Research Institute, University of California
Desiree A. Thayer: Cardiovascular Research Institute, University of California
Hai Huang: Cardiovascular Research Institute, University of California
Thomas B. Kornberg: Cardiovascular Research Institute, University of California
Antoine Royant: Université Grenoble Alpes, Institut de Biologie Structurale (IBS)
Lily Yeh Jan: Cardiovascular Research Institute, University of California
Yuh Nung Jan: Cardiovascular Research Institute, University of California
William A. Weiss: Helen Diller Family Comprehensive Cancer Center, University of California
Xiaokun Shu: University of California

Nature Communications, 2014, vol. 5, issue 1, 1-7

Abstract: Abstract Infrared fluorescent proteins (IFPs) are ideal for in vivo imaging, and monomeric versions of these proteins can be advantageous as protein tags or for sensor development. In contrast to GFP, which requires only molecular oxygen for chromophore maturation, phytochrome-derived IFPs incorporate biliverdin (BV) as the chromophore. However, BV varies in concentration in different cells and organisms. Here we engineered cells to express the haeme oxygenase responsible for BV biosynthesis and a brighter monomeric IFP mutant (IFP2.0). Together, these tools improve the imaging capabilities of IFP2.0 compared with monomeric IFP1.4 and dimeric iRFP. By targeting IFP2.0 to the plasma membrane, we demonstrate robust labelling of neuronal processes in Drosophila larvae. We also show that this strategy improves the sensitivity when imaging brain tumours in whole mice. Our work shows promise in the application of IFPs for protein labelling and in vivo imaging.

Date: 2014
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DOI: 10.1038/ncomms4626

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