Distinct regions within the GluN2C subunit regulate the surface delivery of NMDA receptors

N-methyl-D-aspartate (NMDA) receptors mediate fast excitatory synaptic transmission in the mammalian central nervous system. The activation of NMDA receptors plays a key role in brain development, synaptic plasticity, and memory formation, and is a major contributor to many neuropsychiatric disorder...

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Main Authors: Katarina eLichnerova, Martina eKaniakova, Kristyna eSkrenkova, Ladislav eVyklicky, Martin eHorak
Format: Article
Language:English
Published: Frontiers Media S.A. 2014-11-01
Series:Frontiers in Cellular Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00375/full
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author Katarina eLichnerova
Katarina eLichnerova
Martina eKaniakova
Kristyna eSkrenkova
Ladislav eVyklicky
Martin eHorak
author_facet Katarina eLichnerova
Katarina eLichnerova
Martina eKaniakova
Kristyna eSkrenkova
Ladislav eVyklicky
Martin eHorak
author_sort Katarina eLichnerova
collection DOAJ
description N-methyl-D-aspartate (NMDA) receptors mediate fast excitatory synaptic transmission in the mammalian central nervous system. The activation of NMDA receptors plays a key role in brain development, synaptic plasticity, and memory formation, and is a major contributor to many neuropsychiatric disorders. Here, we investigated the mechanisms that underlie the trafficking of GluN1/GluN2C receptors. Using an approach combining molecular biology, microscopy, and electrophysiology in mammalian cell lines and cultured cerebellar granule cells, we found that the surface delivery of GluN2C-containing receptors is reduced compared to GluN2A- and GluN2B-containing receptors. Furthermore, we identified three distinct regions within the N-terminus, M3 transmembrane domain, and C-terminus of GluN2C subunits that are required for proper intracellular processing and surface delivery of NMDA receptors. These results shed new light on the regulation of NMDA receptor trafficking, and these findings can be exploited to develop new strategies for treating some forms of neuropsychiatric disorders.
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spelling doaj.art-e7e253aa33924e6cbba719a4ebceaf332022-12-21T18:25:25ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022014-11-01810.3389/fncel.2014.00375116568Distinct regions within the GluN2C subunit regulate the surface delivery of NMDA receptorsKatarina eLichnerova0Katarina eLichnerova1Martina eKaniakova2Kristyna eSkrenkova3Ladislav eVyklicky4Martin eHorak5Institute of Physiology, Academy of Sciences of the Czech Republic v.v.i.Faculty of Science, Charles University in PragueInstitute of Physiology, Academy of Sciences of the Czech Republic v.v.i.Institute of Physiology, Academy of Sciences of the Czech Republic v.v.i.Institute of Physiology, Academy of Sciences of the Czech Republic v.v.i.Institute of Physiology, Academy of Sciences of the Czech Republic v.v.i.N-methyl-D-aspartate (NMDA) receptors mediate fast excitatory synaptic transmission in the mammalian central nervous system. The activation of NMDA receptors plays a key role in brain development, synaptic plasticity, and memory formation, and is a major contributor to many neuropsychiatric disorders. Here, we investigated the mechanisms that underlie the trafficking of GluN1/GluN2C receptors. Using an approach combining molecular biology, microscopy, and electrophysiology in mammalian cell lines and cultured cerebellar granule cells, we found that the surface delivery of GluN2C-containing receptors is reduced compared to GluN2A- and GluN2B-containing receptors. Furthermore, we identified three distinct regions within the N-terminus, M3 transmembrane domain, and C-terminus of GluN2C subunits that are required for proper intracellular processing and surface delivery of NMDA receptors. These results shed new light on the regulation of NMDA receptor trafficking, and these findings can be exploited to develop new strategies for treating some forms of neuropsychiatric disorders.http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00375/fullElectrophysiologyion channelglutamate receptorintracellular traffickingcerebellar granule cellsendoplasmic reticulum.
spellingShingle Katarina eLichnerova
Katarina eLichnerova
Martina eKaniakova
Kristyna eSkrenkova
Ladislav eVyklicky
Martin eHorak
Distinct regions within the GluN2C subunit regulate the surface delivery of NMDA receptors
Frontiers in Cellular Neuroscience
Electrophysiology
ion channel
glutamate receptor
intracellular trafficking
cerebellar granule cells
endoplasmic reticulum.
title Distinct regions within the GluN2C subunit regulate the surface delivery of NMDA receptors
title_full Distinct regions within the GluN2C subunit regulate the surface delivery of NMDA receptors
title_fullStr Distinct regions within the GluN2C subunit regulate the surface delivery of NMDA receptors
title_full_unstemmed Distinct regions within the GluN2C subunit regulate the surface delivery of NMDA receptors
title_short Distinct regions within the GluN2C subunit regulate the surface delivery of NMDA receptors
title_sort distinct regions within the glun2c subunit regulate the surface delivery of nmda receptors
topic Electrophysiology
ion channel
glutamate receptor
intracellular trafficking
cerebellar granule cells
endoplasmic reticulum.
url http://journal.frontiersin.org/Journal/10.3389/fncel.2014.00375/full
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