Disease relevance of Grin2d

• MSG treatment (4 mg/g body weight, on postnatal days 1, 3, 5, and 7) produced an important increase of NR2C and NR2D subunit gene expression levels in the hippocampus and striatum of adults rats [1].
• Plugs containing NT-3- secreting fibroblasts and NR2D-expressing HSV-1 amplicons (HSVnr2d) were implanted above the lesion [2].

Psychiatry related information on Grin2d

• Modulation of synaptic strength: subunit expression controls the critical period. Focus on "viral delivery of NR2D subunits reduces Mg2+ block of NMDA receptors and restores NT-3-Induced potentiation of AMPA-kainate responses in maturing rat motoneurons" [3].

High impact information on Grin2d

• NR2D mRNA, present mainly in midbrain structures, peaks around P7 and thereafter decreases to adult levels [4].
• In addition, somatostatin- and cholinergic-, but not enkephalin-positive neurons express NMDAR2D mRNA [5].
• NR2D mRNA localized exclusively to those diencephalic nuclei that have a fourth, distinct pharmacological profile (typified by the midline thalamic nuclei) [6].
• cDNA clones for four different N-methyl-D-aspartate (NMDA) receptor subunits (NMDAR2A-NMDAR2D) were isolated through polymerase chain reactions followed by molecular screening of a rat brain cDNA library [7].
• In contrast, when NMDA receptors were solubilized under nondenaturing conditions, immunoprecipitation followed by quantitative immunoblot analysis of the resulting pellets show that the majority of the NR2D protein is associated with the NR1 subunit [8].

Biological context of Grin2d

• NR1/NR2D NMDA receptors display unusually slow deactivation kinetics which may be critical for their role as extrasynaptic receptors [9].
• A threonine to alanine point mutation has been inserted at amino acid position 692 of the NR2D subunit (T692A) [9].
• Developmental regulation of tyrosine phosphorylation of the NR2D NMDA glutamate receptor subunit in rat central nervous system [10].
• This postnatal switch in voltage control of Mg2+ binding to NMDA receptors may be due to the downregulation of NR2D subunit expression in developing CA1 pyramidal cells [11].
• Using gene chip analyses, RT-PCR, and immunochemistry, we have shown that the NR2D subunit of the NMDA receptor (NMDAR), known to confer resistance to Mg2+ block, also declines in motoneurons during this period [12].

Anatomical context of Grin2d

• Functional NR2B- and NR2D-containing NMDA receptor channels in rat substantia nigra dopaminergic neurones [13].
• Extrasynaptic NR2B and NR2D subunits of NMDA receptors shape 'superslow' afterburst EPSC in rat hippocampus [14].
• Furthermore, NR2B is preferentially and NR2D is exclusively located on extrasynaptic membranes [14].
• The signals for NR2D mRNA appeared transiently in Purkinje cells during the first 8 postnatal days; in adult rats, these were seen in stellate and Golgi cells [15].
• For the nucleus of the solitary tract and in the spinal trigeminal nucleus, we found, in addition to the strong NR2D mRNA signal, moderate expression of the NR2A-C transcripts [16].

Associations of Grin2d with chemical compounds

• As expected of NR2D-containing receptors, these events were not affected by ifenprodil [17].
• Vasopressin cells exhibited 5-fold higher NR2C (32%), approximately half as much NR2B mRNA (39%) and equivalent NR2D (31%) [18].
• Rapid applications of glutamate on outside-out patches containing NR1a/NR2D(T692A) receptors produced macroscopic current deactivations that were about 60-fold faster than wild-type NR1a/NR2D receptors [9].
• Influence of a threonine residue in the S2 ligand binding domain in determining agonist potency and deactivation rate of recombinant NR1a/NR2D NMDA receptors [9].
• The NMDA receptor subunit NR2D and the high-affinity kainate receptor subunit KA1 could not be detected [19].

Regulatory relationships of Grin2d

• Viral delivery of NR2D subunits reduces Mg2+ block of NMDA receptor and restores NT-3-induced potentiation of AMPA-kainate responses in maturing rat motoneurons [12].

Other interactions of Grin2d

• 4. Patches from these cells also contained 'low-conductance' NMDAR channels, with features characteristic of NR2D subunit-containing receptors [17].
• Relative to WKY, mRNA levels for the NR2C and NR2D subunits in the SHR RVLM were significantly lower (0.3- and 0.25-fold less, P< or =0.05), while nNOS was significantly higher (1.76-fold greater, P< or =0.05) [20].
• In the kidney fibroblast (CV1) cell line, we show that in response to 17beta-oestradiol, only ERalpha, not ERbeta, could upregulate transcription from the ERE which is in the 3' untranslated region of the NR2D gene [21].
• In hippocampal neurons cultured for 3 DIV under sustained magnetism, marked mRNA expression was seen for N-methyl-D-aspartate (NMDA) receptor subunits, NR1, NR2A-2C, NR2D, and NR3A [22].
• In addition, the protein phosphatase inhibitor pervanadate (vanadyl hydroperoxide) was found to increase tyrosine phosphorylation of NR2D subunit threefold in brain slices, implying an active cycle of phosphorylation and dephosphorylation in situ [10].

Analytical, diagnostic and therapeutic context of Grin2d

• NR2C and NR2D subunit messenger RNAs was examined by in situ hybridization in neuroendocrine cells of the supraoptic nucleus one month after amygdala kindling to stage 5 seizures [23].
• Reverse transcriptase-polymerase chain reactions (RT-PCR) indicated that levels of NR1, NR2A and NR2D mRNAs reached peak levels between postnatal days 7 (PND 7) and PND 14 [24].
• The expression of NR2D protein by bone cells was shown by immunofluorescence [25].
• NMDA receptor proteins from the thalamus at postnatal days 1, 7, 21, and 49 were solubilized under denaturing conditions and used in immunoprecipitations with these antibodies followed by quantitative immunoblot analysis of NR2D protein in the resulting immunopellets [10].
• Furthermore, immunocytochemistry detected NR2D subunits on hippocampal capillaries [26].

References