Disease relevance of GRIK5

• In the present study, HEK cells expressing the GluR6 +/- KA2 receptor subunit(s) were studied for their susceptibility to toxicity through the kainate receptor by kainate ligands [1].

Psychiatry related information on GRIK5

• Frequency and transmission of glutamate receptors GRIK2 and GRIK3 polymorphisms in patients with obsessive compulsive disorder [2].
• The most surprising negative result is for the GRIK2 (TAA)(n) polymorphism, which has previously shown association with age of onset in four independent populations with Huntington's disease [3].

High impact information on GRIK5

• GRIK4 is the fifth gene shared by human Chr 11 and rat Chr 8, whereas GRIK5 is 1 out of the 12 genes that are located on both human Chr 19 and rat Chr 1 [4].
• A key ligand-binding residue in the KA2 subunit, threonine 675, was mutated to either alanine or glutamate, which eliminated affinity for the receptor ligands kainate and glutamate [5].
• Surface expression of homomeric KA2 receptors lacking a retention/retrieval determinant (KA2-R/A) was also reduced upon mutation of Thr-675 and elimination of the ligand binding site [5].
• Characterization of the rat GRIK5 kainate receptor subunit gene promoter and its intragenic regions involved in neural cell specificity [6].
• When placed downstream of the GRIK5 promoter, a 77-bp sequence from the deleted fragment completely silenced reporter expression in NIH3T3 fibroblasts while attenuating activity in CG-4 cells [6].

Biological context of GRIK5

• GRIK4 and GRIK5 are located on separate chromosomes (Chrs) in all species [4].
• We conclude that SNPs in the gene regions of GRIK3, GRIK4 or GRIK5 do not play a major role in schizophrenia pathogenesis in the Japanese population [7].
• The GRIK2 gene was found to be split into 17 exons, covering about 670 kb of the region [8].
• Recently, Jamain et al. reported that the glutamate receptor 6 (GluR6 or GRIK2) is in linkage disequilibrium with autism [9].

Anatomical context of GRIK5

• KA2 and GluR6 mRNAs were sufficiently abundant for a comparison in the left and right hippocampus between 11 schizophrenics and 13 controls [10].
• We find that KA2 alone does not traffic to the plasma membrane and is retained in the endoplasmic reticulum (ER) [11].
• The GluR5 subunit was expressed in distal dendrites only when GluR6 and KA2 subunits were present, whereas it was restricted to proximal dendrites in the absence of these subunits [12].
• The analysis of subcellular fractions of neocortex revealed that synaptic KARs have a relatively high KA-2 content compared to microsomal ones [13].
• Although KA1 predominantly showed presynaptic localization, KA2 was concentrated to a greater degree on postsynaptic membranes [14].

Associations of GRIK5 with chemical compounds

• Evaluation of a positional candidate gene, the glutamate receptor subunit GRIK5, revealed no mutations [15].
• Immunoblot analysis and electrophysiological recordings failed to demonstrate expression of hGluR1-hGluR4, EAA1/EAA2 proteins and the formation of functional AMPA/kainate receptor channels [16].
• The mRNAs encoding kainic acid (KA) preferring glutamate receptor subunits (GluR5-7, KA1 and KA2) are differentially expressed in rat brain [10].
• Most notably, mutation of Met725 to serine in KA2 increased the affinity of DH by 350-fold; in contrast, mutation of one or more of the residues in GluR5 did not markedly alter DH binding [17].
• Homomeric and heteromeric GluR5 KA receptors were all inhibited to a similar extent by ethanol; however, there was slightly more inhibition of GluR5-R + KA2 receptors [18].

Other interactions of GRIK5

• In contrast, co-expression with GluR6 disrupts ER-retention of KA2 and allows plasma membrane expression [11].
• GluR5/KA-2 receptors had a higher EC50 value than homomeric GluR5 and exhibited a much faster recovery from desensitization [19].
• To elucidate why DH, an agonist, and MSVIII-19, a competitive antagonist, bind selectively to glutamate receptor (GluR) 5 but not to the KA2 KAR subunit, we used molecular dynamics simulations to generate binding models that were tested experimentally in radioligand binding and electrophysiological assays [17].
• The distribution of ionotropic AMPA receptor subunits GluR1-4, kainate receptor subunits GluR5-7 and KA2, delta receptors 1-2, as well as the metabotropic receptor mGluR6 were studied in the frog retina [20].

Analytical, diagnostic and therapeutic context of GRIK5

• Immunoprecipitation studies showed that antibodies to GluR6 and KA2 selectively immunoprecipitated [3H]kainate binding activity, but not 3H-labeled alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) binding activity, from Triton X-100-solubilized rat brain membranes [21].
• We performed a case-control study in 156 patients and 141 controls and the transmission disequilibrium test in 124 parent-offspring trios to search for association between OCD and two kainate receptors, GRIK2 and GRIK3 [2].

References