Disease relevance of Grik2

• Transsynaptic neuronal loss induced in hippocampal slice cultures by a herpes simplex virus vector expressing the GluR6 subunit of the kainate receptor [1].

Psychiatry related information on Grik2

• Experimental basis for the putative role of GluR6/kainate glutamate receptor subunit in Huntington's disease natural history [2].

High impact information on Grik2

• We have now generated mutant mice lacking the kainate-receptor subunit GluR6 [3].
• Our results indicate that kainate receptors containing the GluR6 subunit are important in synaptic transmission as well as in the epileptogenic effects of kainate [3].
• We find that GluR6-deficient mice are less susceptible to systemic administration of kainate, as judged by onset of seizures and by the activation of immediate early genes in the hippocampus [3].
• The homomeric GluR6 glutamate receptor exhibits an outwardly rectifying current-voltage relationship [4].
• In situ hybridizations reveal a pattern of GluR6 gene expression reminiscent of the binding pattern obtained with [3H]kainate [4].

Biological context of Grik2

• Together, these results suggest that GluR6 Q/R site RNA editing may modulate synaptic plasticity and seizure vulnerability [5].
• Alternative splicing is known to regulate surface expression of GluR5 and GluR6 subunits [6].
• Immunohistochemistry and patch clamp on hippocampal neurones in primary culture reveal upregulation of GluR6 protein abundance and kainate-induced currents following treatment with dexamethasone (1 microm) and TGF-beta (1 microm) [7].
• Furthermore, the activation of GluR5 and GluR6 kainate receptor subtypes by endogenous glutamate during seizures may be associated with the drug-resistance phenomenon [8].
• Of the variance in the age of onset of HD that was not accounted for by the CAG repeats, 13% could be attributed to GluR6 genotype variation [9].

Anatomical context of Grik2

• The white matter astrocytes were GluR2/3 and GluR6/7 immunopositive, while the gray matter astrocytes displayed primarily GluR6/7 [10].
• Additionally, synaptic potentiation was significantly reduced in the lateral amygdala of GluR6 but not GluR5 knock-out mice [11].
• However, KAR function is abolished in mice lacking both GluR5 and GluR6 subunits, indicating that KARs in CA1 stratum radiatum interneurons are heteromeric receptors composed of both subunits [12].
• In the presence of GYKI 53655, kainate receptor activation dramatically increases the frequency of spontaneous IPSCs in CA1 pyramidal cells from wild-type, as well as GluR6-/-, mice [13].
• Our findings reveal that KARs comprising GluR5 or GluR6 subunits can either suppress or facilitate glutamatergic excitatory transmission in the SG of acutely prepared adult mouse spinal cord slices [14].

Associations of Grik2 with chemical compounds

• Immunolabeling and Western blot analysis of kainate receptors using antibodies against the GluR6 and KA2 subunits, demonstrated that the immature cortical neurons used in this study express kainate receptor proteins [15].
• Here we show that responses to capsaicin or inflammatory pain were significantly reduced in mice lacking glutamate receptor 5 (GluR5) but not GluR6 subunits [11].
• In this study, we analyse expression of tPA, Grik2, Smarca2 and the transcription factor, Sp1, in mouse cerebellum following acute ethanol treatment [16].
• The ionotropic glutamate receptor subunit GluR6 undergoes developmentally and regionally regulated Q/R site RNA editing that reduces the calcium permeability of GluR6-containing kainate receptors [5].
• Further analysis of cloned GluR6 cDNA revealed that two additional positions, located in transmembrane segment TM1, are diversified by RNA editing to generate either isoleucine (I) or valine (V) in one and tyrosine (Y) or cysteine (C) in the other TM1 position [17].

Regulatory relationships of Grik2

• KA2 was usually coexpressed with GluR6, although with a generally lower level of expression [18].
• In the present study, we show that the GluR6 subunit of KARs is expressed in both substance P- and enkephalin-containing GABAergic projection neurons of the mouse striatum [19].
• Ablation of GluR5 leads to a higher susceptibility of the network to the oscillogenic and epileptogenic effects of kainate, whereas lack of GluR6 prevents kainate-induced gamma oscillations or epileptiform bursts [20].

Other interactions of Grik2

• The white matter showed consistent immunoreactivity for AMPA receptor subunit GluR2/3 and KA receptor subunits GluR6/7 and KA2 [10].
• Additionally, three genes (Ros1, Grik2, and Zfa) were eliminated as possible candidates for vAlb, and several SSLP markers were separated genetically [21].
• In classic fear-memory tests, mice lacking GluR6 but not GluR5 showed a significant reduction in fear memory when measured 3, 7, or 14 d after training [11].
• Using this approach, we obtained a panel of high-affinity antibody fragments that immunoprecipitated both recombinant and native GluRD receptors, but not GluR6, a kainate receptor subunit with a 40% sequence similarity [22].
• 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 [23].

Analytical, diagnostic and therapeutic context of Grik2

• Immunohistochemistry reveals significantly enhanced GluR6 protein abundance at neurones but not at astrocytes in mice [7].
• In coronal, sagittal and horizontal sections fixed with Carnoy solution after dissection from animals decapitated, by contrast, high immunoreactivity was additionally detected to GluR6 subunit in the stratum lucidum of hippocampus [24].
• Pre- and postembedding immunocytochemistry and electron microscopy were used to localize GluR5 and GluR6/7 to specific synaptic contacts at the cone pedicle base [25].
• Immunoblotting analysis revealed heterologous distribution profiles of the non-N-methyl-D-aspartate (NMDA) receptor subunits, GluR1, GluR2 and GluR6, in membrane fractions prepared from murine discrete brain structures including hippocampus [24].
• Nuclease protection assays revealed a large quantitative induction of GluR6 transcripts following retinoic acid treatment [26].

References