Disease relevance of GRIK3

• The aim of our study was to evaluate the association between a history of alcohol withdrawal-induced seizures and delirium tremens, and a functional polymorphism (Ser310Ala) of the GRIK3 gene coding for the glutamatergic kainate receptor subunit GlurR7 in a sample of well-characterized alcoholics compared to controls [1].
• Since glutamate receptors of the kainate subtype have been implicated in neurodegenerative disorders, establishing the precise map position of human GluR-7 subunit is an important step towards evaluating this locus as a candidate for mutations in neurodegenerative disorders [2].

Psychiatry related information on GRIK3

• Frequency and transmission of glutamate receptors GRIK2 and GRIK3 polymorphisms in patients with obsessive compulsive disorder [3].
• Ionotropic glutamate receptor gene GRIK3 SER310ALA functional polymorphism is related to delirium tremens in alcoholics [1].
• We performed a large family-based association study to test if the human kainate receptor GluR7 gene (GRIK3) is associated with bipolar disorder (BP) or recurrent major depressive disorder (R-MDD) [4].

High impact information on GRIK3

• Transcripts of the GluR7 gene are evident in brain areas that bind [3H]kainate and are susceptible to kainate-induced neurotoxicity [5].
• We have performed ligand binding studies with membranes of transfected HeLa cells expressing GluR6 or GluR7 subunits [5].
• PICK1 is required for the control of synaptic transmission by the metabotropic glutamate receptor 7 [6].
• A selective metabotropic glutamate receptor 7 agonist: activation of receptor signaling via an allosteric site modulates stress parameters in vivo [7].
• We describe the isolation of a molluscan (Lymnaea stagnalis) full-length complementary DNA that encodes a mature polypeptide (which we have named Lym-eGluR2) with a predicted molecular weight of 105 kDa that exhibits 44-48% identity to the mammalian kainate-selective glutamate receptor GluR5, GluR6, and GluR7 subunits [8].

Biological context of GRIK3

• Using three single nucleotide polymorphisms (SNP) in GRIK2 and one in GRIK3, we found no evidence for association in case-control or family-based analyses [3].
• We also observed significant haplotype associations in seven SNP pairs in GRIK3 and in four SNP pairs in GRIK4 [9].
• Genotype and allele distributions of GRIK3 T928G polymorphism in schizophrenics were similar to those of controls (p = 0.74 and p = 0.59, respectively) [10].
• One compound, LU 97175, bound to native high affinity kainate receptors and rat GluR5-GluR7 subunits, i.e. low affinity kainate binding sites, with much higher affinities than to AMPA receptors [11].
• Two variation of the EAA5 cDNA were identified which result in amino acid substitutions in the predicted extracellular amino-terminal region; Ser310-->Ala and Arg352-->Gln [12].

Anatomical context of GRIK3

• GRIK3 functional polymorphism was determined using PCR (polymerase chain reaction) of lymphocyte DNA [1].
• Ligand binding studies with membranes of transfected COS-1 cells expressing EAA5 polypeptides demonstrate a rank order of ligand affinity similar to that observed with the rat GluR7 receptor, and a dissociation constant for kainate (2.72 +/- 0.12 nM (n = 3)) that is approximately 20- to 30-fold higher than that observed for the rat GluR7 receptor [12].
• When expressed in Xenopus oocytes GluR6 conducts large agonist-evoked currents, whereas GluR7 lacks measurable currents [13].
• Using somatic cell hybrid analysis, human GluR-7 was localized to chromosome 1 [2].
• Time-dependent effect of kainate-induced seizures on glutamate receptor GluR5, GluR6, and GluR7 mRNA and Protein Expression in rat hippocampus [14].

Associations of GRIK3 with chemical compounds

• 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 [3].
• Family-based and case-control association studies of glutamate receptor GRIK3 Ser310Ala polymorphism in Polish patients and families with alcohol dependence [15].
• The human kainate receptor GluR7 gene contains a thymine (T)/guanine (G) nucleotide variation that determines a serine or alanine at position 310 in the extracellular region of GluR7 receptor subunits [16].

Regulatory relationships of GRIK3

• Finally, we determined the C-terminal half of the L3 domain plus the far C-terminal domain of GluR7 to be responsible for the recently reported reduction of current amplitude seen when GluR7 is coexpressed with GluR6 [13].

Other interactions of GRIK3

• 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 [9].
• IW potently elicited currents from glutamate receptor 5 (GluR5)-expressing cells, but showed no activity on homomeric GluR6 or GluR7 receptors [17].
• Characterization of three novel isoforms of the metabotrobic glutamate receptor 7 (GRM7) [18].
• We detected a significant linkage disequilibrium (LD) indicated by preferential maternal transmission of the GluR7 S310 allele to R-MDD patients (P = 0.012), but not to bipolar I disorder (BPI) patients (P = 1.00) [4].
• Association of the human kainate receptor GluR7 gene (GRIK3) with recurrent major depressive disorder [4].

Analytical, diagnostic and therapeutic context of GRIK3

• GRIK3 functional polymorphism was determined using PCR [15].

References