GluR6 Assays
Background of GluR6
GluR6 is an ionotropic glutamate receptor subunit of the kainate subtype. It can form homomeric receptor channels when expressed in heterologous expression systems. GluR6 undergoes mRNA editing at the Q/R (glutamine/arginine) site located in membrane domain 2, which is believed to line the channel pore of the receptor. The kainate receptor subtype GluR6 is primarily expressed in the excitatory pyramidal cells of the hippocampus.
Fig.1 The structure determined for GluR6 S1S2. (Nanao, 2005)
GluR6 in Diseases
Genetic deletion of GluR6 has revealed important and distinct roles for the GluR6 subunit in synaptic transmission and plasticity in the hippocampus. The disruption of GluR6 editing increases the vulnerability to seizures, suggesting that unedited GluR6 may contribute to seizure generation. More recently, GluR6 has been implicated in other neurological conditions including schizophrenia and Huntington's disease. Previous studies have linked the kainate receptor GluR6 to autism. Mutation screening in individuals with autism identified an M836I amino acid exchange in a highly conserved region of the cytoplasmic C-terminal region of GluR6.
Published Data
| Paper Title | Alternative promoters of the GRIK2 (GluR6) gene in human carcinoma cell lines are regulated by differential methylation of CpG dinucleotides |
| Journal | Genes |
| Published | 2022 |
| Abstract | The ionogenic glutamate receptor 6 (GluR6 or GRIK2) gene is transcribed by two cell type-specific promoters in neuronal and nonneuronal cells, resulting in five different transcriptional variants. This study aimed to explore cell type-specific silencing of these promoters by epigenetic mechanisms. GluR6A transcriptional variants are expressed in the brain, whereas GluR6B is most abundant in tumor cell lines. Neuronal promoters are methylated in non-neuronal cell lines. Bisulfite sequencing revealed that three and 41 CpG sites were methylated in the non-neuronal and neuronal promoters, respectively. The differential activation/silencing of the GluR6 promoter suggests that GluR6 transcriptional variants are involved in tissue-specific biological processes, and its aberrant regulation in tumor cells may lead to different characteristics of tumor cells. |
| Result |
The results demonstrated the differential expression of GluR6/GRIK2 transcriptional variants in neuronal and non-neuronal tumor cells. Transcriptional silencing of GluR6A transcript variants in non-neuronal cells is due to selective methylation of the corresponding promoters in these cells. These observations suggest a non-ion channel role for GluR6 variants in epithelial tumor cell lines and set the stage for investigating the role of non-neuronal GluR6 variants in tumor specificity.
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Fig.2 GluR6 expression in the presence of 5-azacytidine and Trichostatin. (Zhawar, 2022)
References
- Nanao, M.H.; et al. Structure of the kainate receptor subunit GluR6 agonist-binding domain complexed with domoic acid. Proceedings of the National Academy of Sciences. 2005, 102(5): 1708-1713.
- Zhawar, V.K.; et al. Alternative Promoters of GRIK2 (GluR6) Gene in Human Carcinoma Cell Lines Are Regulated by Differential Methylation of CpG Dinucleotides. Genes. 2022, 13(3): 490.
