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Soluble Ectodomain of Neuroligin 1 Decreases Synaptic Activity by Activating Metabotropic Glutamate Receptor 2

Synaptic cell adhesion molecules represent important targets for neuronal activity-dependent proteolysis. Postsynaptic neuroligins (NLs) form trans-synaptic complexes with presynaptic neurexins (NXs). Both NXs and NLs are cleaved from the cell surface by metalloproteases in an activity-dependent man...

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Autores principales: Gjørlund, Michelle D., Carlsen, Eva M. M., Kønig, Andreas B., Dmytrieva, Oksana, Petersen, Anders V., Jacobsen, Jacob, Berezin, Vladimir, Perrier, Jean-François, Owczarek, Sylwia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413576/
https://www.ncbi.nlm.nih.gov/pubmed/28515678
http://dx.doi.org/10.3389/fnmol.2017.00116
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author Gjørlund, Michelle D.
Carlsen, Eva M. M.
Kønig, Andreas B.
Dmytrieva, Oksana
Petersen, Anders V.
Jacobsen, Jacob
Berezin, Vladimir
Perrier, Jean-François
Owczarek, Sylwia
author_facet Gjørlund, Michelle D.
Carlsen, Eva M. M.
Kønig, Andreas B.
Dmytrieva, Oksana
Petersen, Anders V.
Jacobsen, Jacob
Berezin, Vladimir
Perrier, Jean-François
Owczarek, Sylwia
author_sort Gjørlund, Michelle D.
collection PubMed
description Synaptic cell adhesion molecules represent important targets for neuronal activity-dependent proteolysis. Postsynaptic neuroligins (NLs) form trans-synaptic complexes with presynaptic neurexins (NXs). Both NXs and NLs are cleaved from the cell surface by metalloproteases in an activity-dependent manner, releasing a soluble extracellular fragment and membrane-tethered C-terminal fragment. The cleavage of NL1 depresses synaptic transmission, but the mechanism by which this occurs is unknown. Metabotropic glutamate receptor 2 (mGluR2) are located primarily at the periphery of presynaptic terminals, where they inhibit the formation of cyclic adenosine monophosphate (cAMP) and consequently suppress the release of glutamate and decrease synaptic transmission. In the present study, we found that the soluble ectodomain of NL1 binds to and activates mGluR2 in both neurons and heterologous cells, resulting in a decrease in cAMP formation. In a slice preparation from the hippocampus of mice, NL1 inhibited the release of glutamate from mossy fibers that project to CA3 pyramidal neurons. The presynaptic effect of NL1 was abolished in the presence of a selective antagonist for mGluR2. Thus, our data suggest that the soluble extracellular domain of NL1 functionally interacts with mGluR2 and thereby decreases synaptic strength.
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spelling pubmed-54135762017-05-17 Soluble Ectodomain of Neuroligin 1 Decreases Synaptic Activity by Activating Metabotropic Glutamate Receptor 2 Gjørlund, Michelle D. Carlsen, Eva M. M. Kønig, Andreas B. Dmytrieva, Oksana Petersen, Anders V. Jacobsen, Jacob Berezin, Vladimir Perrier, Jean-François Owczarek, Sylwia Front Mol Neurosci Neuroscience Synaptic cell adhesion molecules represent important targets for neuronal activity-dependent proteolysis. Postsynaptic neuroligins (NLs) form trans-synaptic complexes with presynaptic neurexins (NXs). Both NXs and NLs are cleaved from the cell surface by metalloproteases in an activity-dependent manner, releasing a soluble extracellular fragment and membrane-tethered C-terminal fragment. The cleavage of NL1 depresses synaptic transmission, but the mechanism by which this occurs is unknown. Metabotropic glutamate receptor 2 (mGluR2) are located primarily at the periphery of presynaptic terminals, where they inhibit the formation of cyclic adenosine monophosphate (cAMP) and consequently suppress the release of glutamate and decrease synaptic transmission. In the present study, we found that the soluble ectodomain of NL1 binds to and activates mGluR2 in both neurons and heterologous cells, resulting in a decrease in cAMP formation. In a slice preparation from the hippocampus of mice, NL1 inhibited the release of glutamate from mossy fibers that project to CA3 pyramidal neurons. The presynaptic effect of NL1 was abolished in the presence of a selective antagonist for mGluR2. Thus, our data suggest that the soluble extracellular domain of NL1 functionally interacts with mGluR2 and thereby decreases synaptic strength. Frontiers Media S.A. 2017-05-03 /pmc/articles/PMC5413576/ /pubmed/28515678 http://dx.doi.org/10.3389/fnmol.2017.00116 Text en Copyright © 2017 Gjørlund, Carlsen, Kønig, Dmytrieva, Petersen, Jacobsen, Berezin, Perrier and Owczarek. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Gjørlund, Michelle D.
Carlsen, Eva M. M.
Kønig, Andreas B.
Dmytrieva, Oksana
Petersen, Anders V.
Jacobsen, Jacob
Berezin, Vladimir
Perrier, Jean-François
Owczarek, Sylwia
Soluble Ectodomain of Neuroligin 1 Decreases Synaptic Activity by Activating Metabotropic Glutamate Receptor 2
title Soluble Ectodomain of Neuroligin 1 Decreases Synaptic Activity by Activating Metabotropic Glutamate Receptor 2
title_full Soluble Ectodomain of Neuroligin 1 Decreases Synaptic Activity by Activating Metabotropic Glutamate Receptor 2
title_fullStr Soluble Ectodomain of Neuroligin 1 Decreases Synaptic Activity by Activating Metabotropic Glutamate Receptor 2
title_full_unstemmed Soluble Ectodomain of Neuroligin 1 Decreases Synaptic Activity by Activating Metabotropic Glutamate Receptor 2
title_short Soluble Ectodomain of Neuroligin 1 Decreases Synaptic Activity by Activating Metabotropic Glutamate Receptor 2
title_sort soluble ectodomain of neuroligin 1 decreases synaptic activity by activating metabotropic glutamate receptor 2
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5413576/
https://www.ncbi.nlm.nih.gov/pubmed/28515678
http://dx.doi.org/10.3389/fnmol.2017.00116
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