Trafficking and Activity of Glutamate and GABA Receptors: Regulation by Cell Adhesion Molecules

Abstract

The efficient targeting of ionotropic receptors to postsynaptic sites is essential for the function of chemical excitatory and inhibitory synapses, constituting the majority of synapses in the brain. A growing body of evidence indicates that cell adhesion molecules (CAMs), which accumulate at synapses at the earliest stages of synaptogenesis, are critical for this process. A diverse variety of CAMs assemble into complexes with glutamate and GABA receptors and regulate the targeting of these receptors to the cell surface and synapses. Presynaptically localized CAMs provide an additional level of regulation, sending a trans-synaptic signal that can regulate synaptic strength at the level of receptor trafficking. Apart from controlling the numbers of receptors present at postsynaptic sites, CAMs can also influence synaptic strength by modulating the conductivity of single receptor channels. CAMs thus act to maintain basal synaptic transmission and are essential for many forms of activity dependent synaptic plasticity. These activities of CAMs may underlie the association between CAM gene mutations and synaptic pathology and represent fundamental mechanisms by which synaptic strength is dynamically tuned at both excitatory and inhibitory synapses.

Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations

“…Distinct molecular events have been identified for the mechanism and function of CAMs heterooligomerization. The ER exit of the multimeric neuronal synaptic N-Methyl-D-aspartic/aspartate receptor (NMDA) requires two NCAM-subunits to mask its ER retention signal and enhance the PM delivery of the NMDA 51 , 52 . NCAM is also known to modulate the synaptic trafficking of the NMDA receptor 51 , 52 .…”

“…The ER exit of the multimeric neuronal synaptic N-Methyl-D-aspartic/aspartate receptor (NMDA) requires two NCAM-subunits to mask its ER retention signal and enhance the PM delivery of the NMDA 51 , 52 . NCAM is also known to modulate the synaptic trafficking of the NMDA receptor 51 , 52 . The Ig-domain type CAMs neuroplastin and basigin interact with the PM Ca 2+ -ATPases (PMCA) 1–4 subunits and facilitate the PMCA-complex delivery to the cell surface independently of their Ig domains.…”

Distinct Concentration-Dependent Molecular Pathways Regulate Bone Cell Responses to Cobalt and Chromium Exposure from Joint Replacement Prostheses

“…Finally, the up-regulation of glutamate receptor GRIN3A on GB surfaces compared to Ti surfaces may explain the increased mineralization observed on these surfaces in vitro [ 7 ]. Glutamate signaling was indeed shown to increase osteoblast differentiation and function [ 39 ], and the up-regulation of GRIN3A may partly be a result of differential cell adhesion to the different surface roughness of the two materials [ 40 ].…”

Periodicity Pitch Perception Part III: Sensibility and Pachinko Volatility

“…The connectome of neuronal ensembles is orchestrated by neurite guidance, axonal and dendritic branching, synaptogenesis, and synaptic plasticity (Mrsic-Flogel and Bonhoeffer, 2012 ; Rajani et al, 2020 ; Rubio, 2020 ). The assembly of specific neuronal circuits depends on the expression of complementary molecular programs in presynaptic and postsynaptic neurons (Keable et al, 2020 ). Proteins are synthesized locally in different subcellular compartments such as dendritic shafts and spines, triggered by molecular signals such as neurotrophins, brain-derived neurotrophic factor, metabotropic glutamate receptor agonists, or by electrical stimulation (Ribeiro et al, 2019 ; Wu et al, 2019 ).…”