+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Single amino acid residue in the M4 domain of GluN1 subunit regulates the surface delivery of NMDA receptors



Single amino acid residue in the M4 domain of GluN1 subunit regulates the surface delivery of NMDA receptors



Journal of Neurochemistry 123(3): 385-395



N-methyl-D-aspartate (NMDA) receptors are glutamate ion channels that are critically involved in excitatory synaptic transmission and plasticity. The functional NMDA receptor is a heterotetramer composed mainly of GluN1 and GluN2 subunits. It is generally thought that only correctly assembled NMDA receptors can pass the quality control checkpoint in the endoplasmic reticulum (ER) and are transported to the cell surface membranes. The molecular mechanisms underlying these processes remain poorly understood. Using chimeric and mutated GluN1 subunits expressed in heterologous cells, we identified a single amino acid residue within the fourth membrane domain (M4) of GluN1 subunit, L830, that regulates the surface number of NMDA receptors. Our experiments show that this residue is not critical for the interaction between GluN1 and GluN2 subunits or for the formation of functional receptors, but rather that it regulates the forward trafficking of the NMDA receptors. The surface expression of both GluN2A- and GluN2B-containing receptors is regulated by the L830 residue in a similar manner. We also found that the L830 residue is not involved in the trafficking of individually expressed GluN1 subunits. Our data reveal a critical role of the single amino acid residue within the GluN1 M4 domain in the surface delivery of functional NMDA receptors.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 036563664

Download citation: RISBibTeXText

PMID: 22937865

DOI: 10.1111/jnc.12002


Related references

Identification of a single amino acid in GluN1 that is critical for glycine-primed internalization of NMDA receptors. Molecular Brain 6: 36, 2013

Age-Dependent, Subunit Specific Action of Hydrogen Sulfide on GluN1/2A and GluN1/2B NMDA Receptors. Frontiers in Cellular Neuroscience 11: 375, 2017

A Single Amino Acid Residue at Transmembrane Domain 4 of the α Subunit Influences Carisoprodol Direct Gating Efficacy at GABA A Receptors. Journal of Pharmacology and Experimental Therapeutics 362(3): 395-404, 2017

Anti-NMDA receptor encephalitis antibody binding is dependent on amino acid identity of a small region within the GluN1 amino terminal domain. Journal of Neuroscience 32(32): 11082-11094, 2012

Ligand binding domain interface: A tipping point for pharmacological agents binding with GluN1/2A subunit containing NMDA receptors. European Journal of Pharmacology 844: 216-224, 2019

SAP97 blocks the RXR ER retention signal of NMDA receptor subunit GluN1-3 through its SH3 domain. Biochimica et Biophysica Acta 1853(2): 489-499, 2015

An alternating GluN1-2-1-2 subunit arrangement in mature NMDA receptors. Plos one 7(4): E35134, 2012

A single amino acid residue on the alpha5 subunit is essential for ligand selectivity at alpha5beta3gamma2 GABAA receptors. Society for Neuroscience Abstracts 26(1-2): Abstract No -430 2, 2000

GluN1 splice variant control of GluN1/GluN2D NMDA receptors. Journal of Physiology 590(16): 3857-3875, 2012

A single amino acid in the second transmembrane domain of GABA rho receptors regulates channel conductance. Neuroscience Letters 418(2): 205-209, 2007

Inhibition of rat recombinant GluN1/GluN2A and GluN1/GluN2B NMDA receptors by ethanol at concentrations based on the US/UK drink-drive limit. European Journal of Pharmacology 614(1-3): 14-21, 2009

Two N-glycosylation Sites in the GluN1 Subunit Are Essential for Releasing N-methyl-d-aspartate (NMDA) Receptors from the Endoplasmic Reticulum. Journal of Biological Chemistry 290(30): 18379-18390, 2015

A domain within the C-terminal tail regulates cell surface expression of the NMDA NR2B subunit. Society for Neuroscience Abstracts 27(1): 80, 2001

7-Methoxyderivative of tacrine is a 'foot-in-the-door' open-channel blocker of GluN1/GluN2 and GluN1/GluN3 NMDA receptors with neuroprotective activity in vivo. Neuropharmacology 140: 217-232, 2018

Alternative splicing of the C-terminal domain regulates cell surface expression of the NMDA receptor NR1 subunit. Journal of Neuroscience 19(18): 7781-7792, 1999