Understanding neurotransmitter system crosstalk in the brain is a major challenge in neurobiology. Several intracellular and genomic cascades have been identified in this crosstalk. However, the discovery that neurotransmitter receptors are highly diffusive in the plasma membrane of neurons, where they form heterocomplexes with other proteins, has profoundly changed our view of neurotransmitter signaling. Here, we review new insights into neurotransmitter crosstalk at the plasma membrane. We focus on the membrane organization and interactome of the ionotropic glutamate N-methyl-D-aspartate receptor (NMDAR) that plays a central role in excitatory synaptic and network physiology and is involved in the etiology of several major neuropsychiatric disorders. The nanoscale organization and dynamics of NMDAR is a key regulatory process for glutamate synapse transmission, plasticity, and crosstalk with other neurotransmitter systems, such as the monoaminergic ones. The plasma membrane appears to be a prime regulatory compartment for spatial and temporal crosstalk between neurotransmitter systems in the healthy and diseased brain. Understanding the molecular mechanisms regulating membrane neurotransmitter receptor crosstalk will likely open research avenues for innovative therapeutical strategies.
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4 January 2021
Review|
December 18 2020
Regulation of membrane NMDA receptors by dynamics and protein interactions
Mar Petit-Pedrol
,
Mar Petit-Pedrol
Université de Bordeaux, Centre National de la Recherche Scientifique, Interdisciplinary Institute for Neuroscience, Unité Mixte de Recherche 5297, Bordeaux, France
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Laurent Groc
Université de Bordeaux, Centre National de la Recherche Scientifique, Interdisciplinary Institute for Neuroscience, Unité Mixte de Recherche 5297, Bordeaux, France
Correspondence to Laurent Groc: laurent.groc@u-bordeaux.fr
Search for other works by this author on:
Mar Petit-Pedrol
Université de Bordeaux, Centre National de la Recherche Scientifique, Interdisciplinary Institute for Neuroscience, Unité Mixte de Recherche 5297, Bordeaux, France
Laurent Groc
Université de Bordeaux, Centre National de la Recherche Scientifique, Interdisciplinary Institute for Neuroscience, Unité Mixte de Recherche 5297, Bordeaux, France
Correspondence to Laurent Groc: laurent.groc@u-bordeaux.fr
Received:
August 09 2020
Revision Received:
November 19 2020
Accepted:
November 20 2020
Online Issn: 1540-8140
Print Issn: 0021-9525
Funding:
Conseil Régional Aquitaine
(NO AWARD)
© 2020 Petit-Pedrol and Groc
2020
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2021) 220 (1): e202006101.
Article history
Received:
August 09 2020
Revision Received:
November 19 2020
Accepted:
November 20 2020
Citation
Mar Petit-Pedrol, Laurent Groc; Regulation of membrane NMDA receptors by dynamics and protein interactions. J Cell Biol 4 January 2021; 220 (1): e202006101. doi: https://doi.org/10.1083/jcb.202006101
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