Affiliation:
1. Université de Bordeaux, Centre National de la Recherche Scientifique, Interdisciplinary Institute for Neuroscience, Unité Mixte de Recherche 5297, Bordeaux, France
Abstract
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.
Funder
Centre National de la Recherche Scientifique
Agence Nationale de la Recherche
Fondation pour la Recherche Médicale
Human Frontier Science Program
Conseil Régional d'Aquitaine
Labex Bordeaux BRAIN
Publisher
Rockefeller University Press
Cited by
20 articles.
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