Regulation of membrane NMDA receptors by dynamics and protein interactions

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.

Identifying the function of the NMDA NR1C2subunit through its interaction with Magi-2 during inflammatory pain

“…An antibody that recognizes only the NR1 C2 isoform was used in this study. Prior work on NMDAR surface dynamics at the neuronal plasma membrane have shown that NMDAR at the postsynaptic density exhibit confined diffusion with anchoring of receptors but high diffusion with low confinement in the extrasynaptic membrane 57 . These differing NMDAR pools, synaptic vs extrasynaptic, mobile vs immobile, might depend on whether NMDAR contain the NR1 C2' or NR1 C2 subunit.…”

Comparative membrane proteomic analysis of Tritrichomonas foetus isolates

“…In recent years, proteins have been utilized as biomarkers for tissues, cell types, developmental stages, disease states, and as potential targets for drug discovery and interventional approaches. Then, the identification of biomarkers of parasitic infections by differential protein profiling of specific hosts or parasitic molecules is a promising area [48][49][50][51][52] . In this context, membrane proteins have been proposed as interesting candidates in different organisms.…”

TRPM2 enhances ischemic excitotoxicity by associating with PKCγ

“… 2 However, NMDAR antagonists all unfortunately failed to show protective effects in human patients, which was due to the limited understanding of the pathological regulation of NMDAR during ischemic stroke. 3 , 4 Based on their location, NMDARs are divided into synaptic NMDARs (sNMDARs) and extrasynaptic NMDARs (esNMDARs). 5 During ischemic stroke, sNMDARs promote neuron survival, while esNMDARs cause neuronal death.…”