Gephyrin-binding peptides visualize postsynaptic sites and modulate neurotransmission

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Gephyrin-binding peptides visualize postsynaptic sites and modulate neurotransmission. / Maric, Hans Michael; Hausrat, Torben Johann; Neubert, Franziska; Dalby, Nils Ole; Doose, Sören; Sauer, Markus; Kneussel, Matthias; Strømgaard, Kristian.

In: Nature Chemical Biology, Vol. 13, 2246, 2017, p. 153-160.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Maric, HM, Hausrat, TJ, Neubert, F, Dalby, NO, Doose, S, Sauer, M, Kneussel, M & Strømgaard, K 2017, 'Gephyrin-binding peptides visualize postsynaptic sites and modulate neurotransmission', Nature Chemical Biology, vol. 13, 2246, pp. 153-160. https://doi.org/10.1038/nchembio.2246

APA

Maric, H. M., Hausrat, T. J., Neubert, F., Dalby, N. O., Doose, S., Sauer, M., ... Strømgaard, K. (2017). Gephyrin-binding peptides visualize postsynaptic sites and modulate neurotransmission. Nature Chemical Biology, 13, 153-160. [2246]. https://doi.org/10.1038/nchembio.2246

Vancouver

Maric HM, Hausrat TJ, Neubert F, Dalby NO, Doose S, Sauer M et al. Gephyrin-binding peptides visualize postsynaptic sites and modulate neurotransmission. Nature Chemical Biology. 2017;13:153-160. 2246. https://doi.org/10.1038/nchembio.2246

Author

Maric, Hans Michael ; Hausrat, Torben Johann ; Neubert, Franziska ; Dalby, Nils Ole ; Doose, Sören ; Sauer, Markus ; Kneussel, Matthias ; Strømgaard, Kristian. / Gephyrin-binding peptides visualize postsynaptic sites and modulate neurotransmission. In: Nature Chemical Biology. 2017 ; Vol. 13. pp. 153-160.

Bibtex

@article{a68fce64a948420c8a12301cf18a5069,
title = "Gephyrin-binding peptides visualize postsynaptic sites and modulate neurotransmission",
abstract = "γ-Aminobutyric acid type A and glycine receptors are the major mediators of fast synaptic inhibition in the human central nervous system and are established drug targets. However, all drugs targeting these receptors bind to the extracellular ligand-binding domain of the receptors, which inherently is associated with perturbation of the basic physiological action. Here we pursue a fundamentally different approach, by instead targeting the intracellular receptor-gephyrin interaction. First, we defined the gephyrin peptide-binding consensus sequence, which facilitated the development of gephyrin super-binding peptides and later effective affinity probes for the isolation of native gephyrin. Next, we demonstrated that fluorescent super-binding peptides could be used to directly visualize inhibitory postsynaptic sites for the first time in conventional and super-resolution microscopy. Finally, we demonstrate that the gephyrin super-binding peptides act as acute intracellular modulators of fast synaptic inhibition by modulating receptor clustering, thus being conceptually novel modulators of inhibitory neurotransmission.",
author = "Maric, {Hans Michael} and Hausrat, {Torben Johann} and Franziska Neubert and Dalby, {Nils Ole} and S{\"o}ren Doose and Markus Sauer and Matthias Kneussel and Kristian Str{\o}mgaard",
year = "2017",
doi = "10.1038/nchembio.2246",
language = "English",
volume = "13",
pages = "153--160",
journal = "Nature Chemical Biology",
issn = "1552-4450",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Gephyrin-binding peptides visualize postsynaptic sites and modulate neurotransmission

AU - Maric, Hans Michael

AU - Hausrat, Torben Johann

AU - Neubert, Franziska

AU - Dalby, Nils Ole

AU - Doose, Sören

AU - Sauer, Markus

AU - Kneussel, Matthias

AU - Strømgaard, Kristian

PY - 2017

Y1 - 2017

N2 - γ-Aminobutyric acid type A and glycine receptors are the major mediators of fast synaptic inhibition in the human central nervous system and are established drug targets. However, all drugs targeting these receptors bind to the extracellular ligand-binding domain of the receptors, which inherently is associated with perturbation of the basic physiological action. Here we pursue a fundamentally different approach, by instead targeting the intracellular receptor-gephyrin interaction. First, we defined the gephyrin peptide-binding consensus sequence, which facilitated the development of gephyrin super-binding peptides and later effective affinity probes for the isolation of native gephyrin. Next, we demonstrated that fluorescent super-binding peptides could be used to directly visualize inhibitory postsynaptic sites for the first time in conventional and super-resolution microscopy. Finally, we demonstrate that the gephyrin super-binding peptides act as acute intracellular modulators of fast synaptic inhibition by modulating receptor clustering, thus being conceptually novel modulators of inhibitory neurotransmission.

AB - γ-Aminobutyric acid type A and glycine receptors are the major mediators of fast synaptic inhibition in the human central nervous system and are established drug targets. However, all drugs targeting these receptors bind to the extracellular ligand-binding domain of the receptors, which inherently is associated with perturbation of the basic physiological action. Here we pursue a fundamentally different approach, by instead targeting the intracellular receptor-gephyrin interaction. First, we defined the gephyrin peptide-binding consensus sequence, which facilitated the development of gephyrin super-binding peptides and later effective affinity probes for the isolation of native gephyrin. Next, we demonstrated that fluorescent super-binding peptides could be used to directly visualize inhibitory postsynaptic sites for the first time in conventional and super-resolution microscopy. Finally, we demonstrate that the gephyrin super-binding peptides act as acute intracellular modulators of fast synaptic inhibition by modulating receptor clustering, thus being conceptually novel modulators of inhibitory neurotransmission.

U2 - 10.1038/nchembio.2246

DO - 10.1038/nchembio.2246

M3 - Journal article

C2 - 27893705

VL - 13

SP - 153

EP - 160

JO - Nature Chemical Biology

JF - Nature Chemical Biology

SN - 1552-4450

M1 - 2246

ER -

ID: 169435827