Introduction of GRIN2C
Glutamate receptor ionotropic, NMDA 2C (GRIN2C) is a subunit of the N-Methyl-d-aspartate (NMDA) receptors. Generally, functional NMDARs are tetramers consisting of two essential GRIN1 subunits and two regulatory GRIN2 subunits. The four GRIN2 subtypes (GRIN2A-GRIN2D) confer distinct physiological and pharmacological properties to the receptor complex. Firstly, GRIN2C shows relatively unique channel properties, including low conductance, open probability and sensitivity to magnesium. Secondly, compared to the other subunits of NMDA receptors, the distribution of GRIN2C is much more restricted. It is highly enriched in the cerebellum, thalamus, and olfactory bulb. It has also been found in other areas of the brain including the cortex and hippocampus in spite of being minimally detected.
|Basic Information of GRIN2C|
|Protein Name||Glutamate receptor ionotropic, NMDA 2C|
|Gene Name||GRIN2C, NMDAR2C|
|Organism||Homo sapiens (Human)|
Functions of GRIN2C Membrane Protein
The unique channel properties and expression patterns indicate that GRIN2C-containing NMDARs have a specific function in the brain. This subunit has been found to play a role in neuronal development and neuroprotection, as well as being implicated in ischemia, schizophrenia, and epilepsy. For instance, lower expression of GRIN2C subunit has been reported in postmortem brains from schizophrenia patients. Moreover, studies reported that GRIN2C-containing receptors may have preferential involvement in psychotic states produced by ketamine. Using GRIN2C knockout mice, it has been demonstrated that GRIN2C promotes neuroprotective effects following ischemia. Using specific positive allosteric modulators, agonists, or antagonists of GRIN2C-containing receptors, such as CIQ, the therapeutic potential of this subunit in different human brain disorders can be exploited.
Fig.1 NMDA subunit structure and topology. (Sanz-Clemente, 2013)
Application of GRIN2C Membrane Protein in Literature
This study investigated the role of the GluN2C receptor in the heterozygote Tsc1+/− mice. They have identified functional upregulation of cortical GluN2C-containing NMDARs and that specific GlN2C/D antagonists block seizures in these mice. These results showed that GluN2C was a promising molecular target to treat epilepsy in TSC patients.
This study investigated the effect of CIQ, a positive allosteric modulator selective for GluN2C/GluN2D-containing NMDA receptors, on impairment in prepulse inhibition, hyperlocomotion, impairment in working memory, and stereotypy by i.p. administration of MK-801 and methamphetamine. The results suggested that facilitation of GluN2C/GluN2D-containing NMDAR was a potential therapeutic strategy for treating positive and cognitive symptoms in schizophrenia.
This study investigated the role of the NMDA receptor GluN2C subunit in brain functions. The results demonstrated that loss of GluN2C subunit led to cortical excitatory-inhibitory imbalance and abnormal neuronal oscillations associated with neurodevelopmental disorders.
This study investigated the role of GluN2C following ischemia using both in vivo and in vitro experimental models of ischemia. The results showed that GluN2C was upregulated to promote neuronal survival following ischemia and that GluN2C might be a useful target for neuroprotection.
This study described the design, synthesis, and characterization of a novel series of pyrrolidinones that selectively potentiate only GluN2C-containing NMDARs.
GRIN2C Preparation Options
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