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Molecular determinants for the strictly compartmentalized expression of kainate receptors in CA3 pyramidal cells

Distinct subtypes of ionotropic glutamate receptors can segregate to specific synaptic inputs in a given neuron. Using functional mapping by focal glutamate uncaging in CA3 pyramidal cells (PCs), we observe that kainate receptors (KARs) are strictly confined to the postsynaptic elements of mossy fib...

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Autores principales: Fièvre, Sabine, Carta, Mario, Chamma, Ingrid, Labrousse, Virginie, Thoumine, Olivier, Mulle, Christophe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052629/
https://www.ncbi.nlm.nih.gov/pubmed/27669960
http://dx.doi.org/10.1038/ncomms12738
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author Fièvre, Sabine
Carta, Mario
Chamma, Ingrid
Labrousse, Virginie
Thoumine, Olivier
Mulle, Christophe
author_facet Fièvre, Sabine
Carta, Mario
Chamma, Ingrid
Labrousse, Virginie
Thoumine, Olivier
Mulle, Christophe
author_sort Fièvre, Sabine
collection PubMed
description Distinct subtypes of ionotropic glutamate receptors can segregate to specific synaptic inputs in a given neuron. Using functional mapping by focal glutamate uncaging in CA3 pyramidal cells (PCs), we observe that kainate receptors (KARs) are strictly confined to the postsynaptic elements of mossy fibre (mf) synapses and excluded from other glutamatergic inputs and from extrasynaptic compartments. By molecular replacement in organotypic slices from GluK2 knockout mice, we show that the faithful rescue of KAR segregation at mf-CA3 synapses critically depends on the amount of GluK2a cDNA transfected and on a sequence in the GluK2a C-terminal domain responsible for interaction with N-cadherin. Targeted deletion of N-cadherin in CA3 PCs greatly reduces KAR content in thorny excrescences and KAR-EPSCs at mf-CA3 synapses. Hence, multiple mechanisms combine to confine KARs at mf-CA3 synapses, including a stringent control of the amount of GluK2 subunit in CA3 PCs and the recruitment/stabilization of KARs by N-cadherins.
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spelling pubmed-50526292016-10-21 Molecular determinants for the strictly compartmentalized expression of kainate receptors in CA3 pyramidal cells Fièvre, Sabine Carta, Mario Chamma, Ingrid Labrousse, Virginie Thoumine, Olivier Mulle, Christophe Nat Commun Article Distinct subtypes of ionotropic glutamate receptors can segregate to specific synaptic inputs in a given neuron. Using functional mapping by focal glutamate uncaging in CA3 pyramidal cells (PCs), we observe that kainate receptors (KARs) are strictly confined to the postsynaptic elements of mossy fibre (mf) synapses and excluded from other glutamatergic inputs and from extrasynaptic compartments. By molecular replacement in organotypic slices from GluK2 knockout mice, we show that the faithful rescue of KAR segregation at mf-CA3 synapses critically depends on the amount of GluK2a cDNA transfected and on a sequence in the GluK2a C-terminal domain responsible for interaction with N-cadherin. Targeted deletion of N-cadherin in CA3 PCs greatly reduces KAR content in thorny excrescences and KAR-EPSCs at mf-CA3 synapses. Hence, multiple mechanisms combine to confine KARs at mf-CA3 synapses, including a stringent control of the amount of GluK2 subunit in CA3 PCs and the recruitment/stabilization of KARs by N-cadherins. Nature Publishing Group 2016-09-27 /pmc/articles/PMC5052629/ /pubmed/27669960 http://dx.doi.org/10.1038/ncomms12738 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Fièvre, Sabine
Carta, Mario
Chamma, Ingrid
Labrousse, Virginie
Thoumine, Olivier
Mulle, Christophe
Molecular determinants for the strictly compartmentalized expression of kainate receptors in CA3 pyramidal cells
title Molecular determinants for the strictly compartmentalized expression of kainate receptors in CA3 pyramidal cells
title_full Molecular determinants for the strictly compartmentalized expression of kainate receptors in CA3 pyramidal cells
title_fullStr Molecular determinants for the strictly compartmentalized expression of kainate receptors in CA3 pyramidal cells
title_full_unstemmed Molecular determinants for the strictly compartmentalized expression of kainate receptors in CA3 pyramidal cells
title_short Molecular determinants for the strictly compartmentalized expression of kainate receptors in CA3 pyramidal cells
title_sort molecular determinants for the strictly compartmentalized expression of kainate receptors in ca3 pyramidal cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052629/
https://www.ncbi.nlm.nih.gov/pubmed/27669960
http://dx.doi.org/10.1038/ncomms12738
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