Disease relevance of Gria4

• We have isolated approximately 5 kb of the rat GluR4 promoter region and analyzed its capacity to drive expression of a luciferase reporter gene in transfected rat cortical neurons and glia, and C6 glioma cells [1].
• To demonstrate the cellular distributions of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor subunits (GluR1, GluR2/3, and GluR4) in the intrastriatal grafts of a rat model of Parkinson's disease, immunocytochemistry was performed in 6-hydroxydopamine rats with intrastriatal transplants of fetal ventral mesencephalon (VM) [2].
• In contrast, reactive microglia expressed GluR4 and NR1 subunits, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), and NMDA receptor subtypes, respectively, with maximal expression observed between 3 and 7 days after ischemia [3].
• In the ganglion neurons, GluR2/R3 and GluR4 may represent reserve intracytoplasmic pools of receptor subunits in transit to the postsynaptic sites [4].

High impact information on Gria4

• Here we report the cloning and expression of a functional rat glutamate receptor subunit cDNA, GluR6, which has a very different pharmacology from that of the GluR1-GluR4 class [5].
• When expressed in Xenopus oocytes the homomeric GluR6 receptor is activated by kainate, quisqualate and L-glutamate but not by AMPA, and the apparent affinity for kainate is higher than for receptors from the GluR1-GluR4 class [5].
• Sequence homology between complementary DNA clones encoding non-NMDA glutamate receptor subunits reveals at least two subunit classes: the GluR1 to GluR4 class and the GluR5 class [5].
• Cloned AMPA receptors carrying the "flop" splice variants of glutamate receptor subtype C (GluR-C) and GluR-D are shown to have desensitization time constants of around 1 millisecond, whereas those with the "flip" variants are about four times slower [6].
• These findings suggest that rapid desensitization of AMPA receptors can be regulated by the expression and alternative splicing of GluR-D gene transcripts [6].

Biological context of Gria4

• Screening a rat cerebellar cDNA library, we have now identified a third type of transcript derived from GluR-4 gene by differential RNA processing [7].
• An intron within the 5'-untranslated region and Sp1, IK2 and E-box sites are conserved in the rat, mouse and human GluR4 promoters [1].
• The rapid kinetics of GluR4-rich AMPA receptors we suggest indicate that cortical descending control may be more temporally precise than previously recognized [8].
• GluR3-expressing glia appeared to be more susceptible to apoptosis than GluR4-expressing cells [9].
• Activity-driven PKA phosphorylation of GluR4 was necessary and sufficient to relieve a retention interaction and drive receptors into synapses [10].

Anatomical context of Gria4

• GluR1-GluR4 AMPA-selective subunits were all expressed in cochlear nucleus neurons; however, the subunits expressed in identified cells varied with the cell type [11].
• Ultrastructurally, GluR subunit immunoreactivities are localized within cell bodies, dendrites and dendritic spines of specific subsets of neurons and, in the case of GluR1 and GluR4, in some populations of astrocytes [12].
• In several brain regions, astrocytes show GluR4 immunoreactivity [12].
• In the monkey, immunoreactivity for GluR4 in interneurons was stronger than for GluR1 [13].
• Low levels of GluR1, GluR4 and GluR6 expression were detected in various tissues of the cochlea during development [14].

Associations of Gria4 with chemical compounds

• In conclusion our results confirm the existence of glutamate ionotropic receptors of the AMPA type in primary astroglial cultures and suggest that GluR-4 is the main AMPA receptor subunit expressed in non-neuronal cells of the central nervous system [15].
• Expression of AMPA receptor subunits (GluR1-GluR4) in gonadotrophin-releasing hormone neurones of young and middle-aged persistently oestrous rats during the steroid-induced luteinising hormone surge [16].
• However, GluR3 mRNA was preferentially expressed by neurons coexpressing substance P and enkephalin and GluR4 mRNA was not detected in identified medium spiny neurons [17].
• Deletion of the GluR4 transcriptional initiation region decreased luciferase activity in neurons, but increased activity in C6 cells, suggesting that regulatory elements governing neuronal expression reside in this region [1].
• GluR4 mRNA levels did not differ between K10 and K25, although they were reduced by chronic exposure to NMDA [18].

Physical interactions of Gria4

• Samples of paraventricular and lateral geniculate nuclei stained with GluR1 and of reticular nucleus as well as ventrobasal complex stained with GluR4 were used for the ultrastructural study [19].

Regulatory relationships of Gria4

• GluR4 expression was maintained at higher levels at 08.00 and 12.00 h in young rats; although the percentage of Fos-positive GnRH neurones expressing GluR4 peaked at 12.00 h in young rats, it showed little change in MA-PE rats [16].
• The nested PCR specific for GluR1-GluR4 showed that rat striatal NADPH-d(+) neurons expressed twice as much GluR1 mRNA as NADPH-d(-) neurons did [20].
• During the following 2 weeks, GluR2/3 receptors were downregulated in exchange for GluR4 receptors [21].
• Immunoreactivity for the GluR4 antibody was least abundant in the reticular formation and GluR4 immunoreactive cells were least likely to co-express calretinin [22].

Other interactions of Gria4

• Granule cells, previously not known to receive glutamatergic input, expressed GluR2 and GluR4 subunits [11].
• The data suggest that the composition of GluR1-GluR4 subunits on neurons in the cochlear nucleus may be related to presynaptic input; moreover, heterogeneous patterns of expression of the GluR3 subunit, in addition, suggest that variability in mRNA levels within one population of morphologically defined cells is present [11].
• GluR4 immunoreactivity showed heavy staining in the external plexiform and olfactory nerve layers with localization to mitral cells, mitral/tufted dendritic processes, and olfactory nerve glial processes [23].
• We have isolated cDNAs encoding a glutamate receptor subunit, designated GluR5, displaying 40%-41% amino acid identity with the kainate/AMPA receptor subunits GluR1, GluR2, GluR3, and GluR4 [24].
• Half-lives were found to be 18 +/- 5 h and 23 +/- 8 h for the AMPA receptor subunits GluR2/3 and GluR4, respectively, and 16 +/- 5 h for NR2A [25].

Analytical, diagnostic and therapeutic context of Gria4

• Under our experimental conditions employed, however, Western blotting assays failed to confirm the expression of receptor proteins for GluR1, GluR2/3 and GluR4 subunits in the adrenal cortex, adrenal medulla, adenohypophysis and neurohypophysis [26].
• The following GluRs were cloned by isoform-specific RT-PCR from rat heart ribonucleic acid (RNA): GluR 1, GluR 3, GluR 4, GIuR 7, Ka 1, and Ka 2 [27].
• Furthermore, in situ hybridization histochemistry revealed that the GluR-4c transcripts are preferentially expressed in cerebellar granule cells and Bergmann glial cells, whereas the expression of GluR-4 flip mRNAs is restricted to Bergmann glial cells [7].
• Three transcripts of 6.2, 4.2, and 3.0 kilobases (kb) derived from the GluR-4 gene were identified on Northern blots containing total RNA prepared from different brain regions, using a cDNA probe or an oligonucleotide corresponding to the N-terminal region common to all transcripts [7].
• Image analysis showed a significant decrease in the intensity of immunohistochemical labeling for the GluR2/3 and GluR4 subunits in motoneurons, although most motoneurons were still immunopositive for these 2 subunits after axotomy [28].

References