TY  - JOUR
AU  - Zhang, William H
AU  - Herde, Michel K
AU  - Mitchell, Joshua A
AU  - Whitfield, Jason H
AU  - Wulff, Andreas B
AU  - Vongsouthi, Vanessa
AU  - Sanchez-Romero, Inmaculada
AU  - Gulakova, Polina E
AU  - Minge, Daniel
AU  - Breithausen, Björn
AU  - Schoch, Susanne
AU  - Janovjak, Harald
AU  - Jackson, Colin J
AU  - Henneberger, Christian
TI  - Monitoring hippocampal glycine with the computationally designed optical sensor GlyFS.
JO  - Nature chemical biology
VL  - 14
IS  - 9
SN  - 1552-4450
CY  - Basingstoke
PB  - Nature Publishing Group
M1  - DZNE-2020-06473
SP  - 861-869
PY  - 2018
AB  - 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.
KW  - Animals
KW  - Cells, Cultured
KW  - Fluorescence Resonance Energy Transfer
KW  - Fluorescent Dyes: chemical synthesis
KW  - Fluorescent Dyes: chemistry
KW  - Glycine: analysis
KW  - HEK293 Cells
KW  - Hippocampus: chemistry
KW  - Humans
KW  - Male
KW  - Optical Imaging
KW  - Rats
KW  - Rats, Wistar
KW  - Fluorescent Dyes (NLM Chemicals)
KW  - Glycine (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:30061718
DO  - DOI:10.1038/s41589-018-0108-2
UR  - https://pub.dzne.de/record/140151
ER  -