Disease relevance of Gria3

• An autoantibody against the GluR3 subunit of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors is implicated in the pathophysiology of Rasmussen's encephalitis [1].
• This sequence significantly reduced levels of GluR3 protein and protected neuroblastoma x spinal cord (NSC-34) cells against death induced by the AMPA receptor-specific agonist (S)-5-fluorowillardiine [2].
• In the present study, we immunized four mouse strains (BALB/c, C3H/HeJ, SJL/J and C57BL/6) with the GluR3B peptide, and investigated the development of (1) anti-GluR3B antibodies; (2) anti-GluR3 T cells; (3) clinical symptoms and abnormal behaviour; (4) brain pathology [3].

High impact information on Gria3

• Synaptic transmission and plasticity in the absence of AMPA glutamate receptor GluR2 and GluR3 [4].
• Two rabbits immunized with a portion of glutamate receptor (GluR) subunit GluR3 (amino acids 245-457) exhibited seizure-like behaviors, suggesting that antibodies to GluR3 may modulate neuronal excitability [5].
• Here, we examine the apparent difference in the regulation of these AMPA receptor subunits by attempting to rescue LTD in GluR2(-/-) Purkinje cells with WT and mutant GluR2 and GluR3 subunits [6].
• Finally, computer modeling suggested that the dimer interface, largely formed by N1, is highly hydrophobic in GluR3, whereas in GluR6 it contains electrostatic interactions, hence offering an explanation for the subtype assembly specificity conferred by this region [7].
• Moreover, a deletion in GluR3 corresponding to the hotfoot mouse mutation of the glutamate receptor delta2, covering part of N2, N3, and N4, impaired both homomeric and heteromeric oligomerization, thus explaining the null-like mouse phenotype [7].

Biological context of Gria3

• Recent proteomic analysis within our group on the copper zinc superoxide dismutase (SOD1)(G93A) transgenic mouse model of familial ALS (FALS) reveals a potentially deleterious upregulation of GluR3 in spinal cord compared to that in wild-type littermates [2].
• We investigated the in vivo pathogenic potential of murine autoimmunity to peptides of the glutamate/AMPA receptor subunit 3 (GluR3) [3].
• GluR-C KOs displayed a blunted, cue-induced reinstatement response and alcohol deprivation effect, when compared with wild-type controls; however, no differences between genotypes could be observed regarding ethanol self-administration under operant or home cage drinking conditions [8].

Anatomical context of Gria3

• We quantified the intensity of GluR3 immunoreactivity in interneuron subtypes defined by their calcium-binding protein content [1].
• These results suggest that interference with the GluR3 component of the AMPA receptor assembly may be a novel strategy for controlling excitotoxic destruction of motor neurons and may lead to new therapeutic opportunities for the treatment of human ALS [2].
• We developed and characterized a GluR3-specific monoclonal antibody and quantified the cellular distribution of GluR3 in CA1 of the rat hippocampus [1].
• GluR3 immunoreactivity was detected in all pyramidal neurons and astrocytes and in most interneurons [1].
• The expression of GluR3 flip was increased in the cortical area and caudate putamen of mu-opioid receptor knockout mice [9].

Associations of Gria3 with chemical compounds

• To test this possibility, the alanine in GluR1 was converted to a phenylalanine, which extended the subunit specificity from GluR3 to the modified GluR1 [10].
• In the voltage clamp studies we investigated the effects of anandamide on recombinant AMPA GluR3 subunit currents generated by kainic acid in oocytes expressing the AMPA glutamate receptor [11].

Other interactions of Gria3

• The AMPA glutamate receptor (AMPAR) subunits GluR2 and GluR3 are thought to be important for synaptic targeting/stabilization of AMPARs and the expression of hippocampal long-term depression (LTD) [4].
• Electron microscopy revealed enriched GluR3 immunoreactivity in parvalbumin-containing perikarya at cytoplasmic and postsynaptic sites [1].
• We detected a slight but statistically significant decrease of the AMPA receptor subunits GluR3 and GluR4 only in end stage disease animals [12].
• Our findings suggest that the somata of these interneurons are enriched in GluR3, which may render them vulnerable to pathological states such as epilepsy and Rasmussen's encephalitis [1].

Analytical, diagnostic and therapeutic context of Gria3

• Western blot analysis, however, did not reveal a significant reduction in GluR3 protein levels in whole extracts of the lumbar spinal cord [2].
• Quantitative PCR studies suggested the pronounced expression of PEPA-preferring AMPA receptor subunits (GluR3 and GluR4) and a splice variant (flop) in the mPFC [13].

References