Disease relevance of Grin2c

• Therefore the development of drugs selectively inhibiting NR2C may prove beneficial in the treatment of stroke and traumatic brain injuries [1].

Psychiatry related information on Grin2c

• However, NR2C-/- mice showed normal light-dark (LD)-entrained locomotor activity rhythms and free-running rhythms under constant darkness and also exhibited normal reentrainment to 6-hr LD shifts and phase delays with single light pulses [2].

High impact information on Grin2c

• To develop a cell type-specific and temporal regulation system of gene targeting in the cerebellum, we used the NMDA-type glutamate receptor GluRepsilon3 subunit gene and Cre recombinase-progesterone receptor fusion (CrePR) gene in combination [3].
• Both NR2A- and NR2C-deficient mice showed no impaired movements in the motor coordination tasks tested [4].
• It is expressed in the forebrain and in cerebellar granule cells at early postnatal stages and selectively repressed in the cerebellum after the second postnatal week, where it is replaced by the NR2C subunit [5].
• Comparison of intron positions in genes encoding different members of the glutamate receptor family confirms a close evolutionary relationship of the NR2C and NMDAR1 subunit genes [6].
• Gene structure of the murine N-methyl D-aspartate receptor subunit NR2C [6].

Biological context of Grin2c

• N-methyl-D-aspartate receptor subtype 2C is not involved in circadian oscillation or photoic entrainment of the biological clock in mice [2].
• The synaptic portion of NMDA receptors measured using MK-801 blockade was roughly 50% in all genotypes at DIV8, and this percentage became slightly larger in NR2A-/- and NR2C-/- neurons at DIV12 [7].
• The murine N-methyl D-aspartate receptor subunit NR2C (epsilon-3) is encoded by a unique gene composed of 12 translated and three 5'-untranslated exons that spread over approximately 20 kilobases of genomic sequence [6].
• The resultant increase in intracellular Ca2+ activated Ca2+/calmodulin-dependent calcineurin phosphatase and blocked NR2C mRNA upregulation [8].
• Our data demonstrate that the SpS neurons of layer 4 functionally express NR2C subunits; this is the likely explanation for their ability to generate large NMDAR-mediated EPSPs that are effective at resting potential, without previous depolarization [9].

Anatomical context of Grin2c

• N-Methyl-D-aspartate receptor subunits NR1 and NR2C are overexpressed in the inferior colliculus of audiogenic mice [10].
• However, some distinct differences were observed: The inferior olive preferentially expresses flop variants of AMPA receptors, GluR7 is more abundant in the pre-Bötzinger complex than in the other nuclei, and NR2C is most prominent in the nucleus of the solitary tract [11].
• In contrast to the ex vivo binding, in vitro [(11)C]L-703,717 binding displayed a similar binding characteristic between GluRepsilon3-deficient and wild-type mice with highly specific localizations in the hippocampus and cerebral cortex [12].
• In the neocortex of transgenic mice in which a beta-galactosidase (lacZ) indicator gene was controlled by the NR2C promoter, the lacZ indicator was densely expressed in layer 4 [9].

Associations of Grin2c with chemical compounds

• Cholinergic cells in the nucleus basalis of mice express the N-methyl-d-aspartate-receptor subunit NR2C and its replacement by the NR2B subunit enhances frontal and amygdaloid acetylcholine levels [13].
• A partial reduction in Ca(2+) elevation was observed in both NR2A-/- and NR2C-/- mice when high concentrations (100 or 300 microM) of NMDA were applied [2].
• The expression of NR2C subunit containing receptors was supported by the decreased Mg(2+) sensitivity of NMDA receptors at DIV13 in +/+ but not in NR2C-/- cells [7].

Regulatory relationships of Grin2c

• Thus, NR2A/NR2C subunits and particularly their C termini regulate synaptic NMDA receptor activation and function by enhancing channel open probability, which is critical for long-term potentiation induction [14].
• Neuronal depolarization controls brain-derived neurotrophic factor-induced upregulation of NR2C NMDA receptor via calcineurin signaling [8].

Other interactions of Grin2c

• GluRepsilon3 subunit mRNAs were not synthesized by NE-7C2 cells and increased numbers of messages from the GluRepsilon2 gene were detected only after neural network formation [15].
• Consistent with the known functional localization, GluRepsilon1, GluRepsilon3, and GluRzeta1 are, thus, anatomically concentrated at the mossy fibre-granule cell synapse [16].
• The NR2A and NR2C subunits thus contribute to distinct NMDA receptor-mediated excitatory transmission in mossy fiber-granule cell synapses in the mature cerebellum [4].
• Regulation of the murine NMDA-receptor-subunit NR2C promoter by Sp1 and fushi tarazu factor1 (FTZ-F1) homologues [17].
• PPDC was identified as a new class of NMDA-receptor antagonist because it has a mode of action different from that of the previous antagonists; it selectivly binds the GluRepsilon3/GluRzeta1 and GluRepsilon4/GluRzeta1 subtype receptors in an agonist-independent allosteric manner [18].

References