Monitoring hippocampal glycine with the computationally designed optical sensor GlyFS
| Autor: | Jason H. Whitfield, Joshua A. Mitchell, Colin J. Jackson, Vanessa Vongsouthi, Inmaculada Sanchez-Romero, Andreas B. Wulff, Björn Breithausen, William H. Zhang, Harald Janovjak, Susanne Schoch, Daniel Minge, Polina E. Gulakova, Michel K. Herde, Christian Henneberger |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Glycine Hippocampus 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine ddc:570 Extracellular Fluorescence microscope Fluorescence Resonance Energy Transfer Animals chemistry [Hippocampus] Humans Rats Wistar Neurotransmitter Molecular Biology Cells Cultured Fluorescent Dyes chemistry.chemical_classification chemistry [Fluorescent Dyes] Optical Imaging Cell Biology Amino acid Rats 030104 developmental biology Förster resonance energy transfer HEK293 Cells chemistry Synaptic plasticity Biophysics Fluorescent glucose biosensor 030217 neurology & neurosurgery chemical synthesis [Fluorescent Dyes] analysis [Glycine] |
| Zdroj: | Nature chemical biology 14(9), 861-869 (2018). doi:10.1038/s41589-018-0108-2 |
| DOI: | 10.1038/s41589-018-0108-2 |
| Popis: | Fluorescent sensors are an essential part of the experimental toolbox of the life sciences, where they are used ubiquitously to visualize intra- and extracellular signaling. In the brain, optical neurotransmitter sensors can shed light on temporal and spatial aspects of signal transmission by directly observing, for instance, neurotransmitter release and spread. Here we report the development and application of the first optical sensor for the amino acid glycine, which is both an inhibitory neurotransmitter and a co-agonist of the N-methyl-D-aspartate receptors (NMDARs) involved in synaptic plasticity. Computational design of a glycine-specific binding protein allowed us to produce the optical glycine FRET sensor (GlyFS), which can be used with single and two-photon excitation fluorescence microscopy. We took advantage of this newly developed sensor to test predictions about the uneven spatial distribution of glycine in extracellular space and to demonstrate that extracellular glycine levels are controlled by plasticity-inducing stimuli. |
| Databáze: | OpenAIRE |
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