Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamate released in the basal ganglia is involved in the expression of clinical symptoms of neurodegenerative diseases like Parkinson's or Huntington's. Neostriatal neurons are the targets of glutamatergic inputs derived from the cortex and the thalamus acting via AMPA-type as well as other glutamate receptors. To determine the location of subunits of the AMPA subclass of glutamate receptors (GluR) in the rat neostriatum, we applied multiple immunocytochemical techniques using anti-peptide antibodies against the GluR1, GluR2/3, and GluR4 subunits at both the light and electron microscopic levels. All medium spiny efferent neurons, some of which were identified as striatonigral neurons, displayed immunoreactivity for GluR1 and GluR2/3 subunits. Double immunofluorescence revealed that at least 70-90% of parvalbumin-immunopositive GABAergic interneurons were immunoreactive for each of GluR1, GluR2/3, or GluR4 subunits and that at least 40% of choline acetyltransferase-immunopositive cholinergic interneurons were immunopositive for GluR1 or GluR4 subunits. The majority of nitric oxide synthase-immunopositive neurons had no detectable immunoreactivity for any of the AMPA receptor subunits. Electron microscopic analysis confirmed the presence of immunoreactivity for GluR1 and GluR2/3 in the perikarya of spiny neurons and interneurons and GluR4 in perikarya of interneurons only. GluR1 and GluR2/3 subunits were detected in dendrites and spines. A significant population of extrasynaptic receptors was revealed by pre-embedding immunogold labeling along the plasma membranes of perikarya, dendrites, and spines. Receptors were concentrated in the postsynaptic membrane specialization of asymmetrical synapses, as revealed by the postembedding immunogold method. Quantitative analysis demonstrated that immunoreactivity for the GluR1 and GluR2/3 subunits is higher at the periphery than at the middle of the postsynaptic membrane specialization. Our results demonstrate that AMPA receptor subunits are distributed widely and heterogeneously among striatal neurons and are concentrated on the postsynaptic membrane of asymmetrical synaptic specializations, although extrasynaptic receptors are also present.
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PMID:Cellular, subcellular, and subsynaptic distribution of AMPA-type glutamate receptor subunits in the neostriatum of the rat. 898 3

Glutamatergic neurotransmission in the subthalamic nucleus (STN) and in the output nuclei of the basal ganglia is critical in the expression of basal ganglia function, and increased glutamate transmission in these nuclei has been implicated in the pathology of Parkinson's disease. In order to determine the precise spatial relationship of subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA) glutamate receptors to nerve terminals enriched in glutamate or gamma-aminobutyric acid (GABA) in one of the output nuclei, the entopeduncular nucleus (EP), and the STN, postembedding immunolabelling for glutamate receptor subunits and for glutamate and GABA was carried out in the rat. Immunolabelling for the AMPA glutamate receptor subunits 1, 2/3, and 4 (GluR1, GluR2/3, and GluR4) and the NMDA receptor subunit 1 (NR1) was localized predominantly within asymmetrical synapses in both the EP and STN. Quantitative analysis revealed that, on average for the whole population, each of the receptor subunits was evenly distributed along the synaptic specialization. Multiple AMPA receptor subunits and the GluR2/3 and NMDA (NR1) subunits were co-localized within individual synapses. The combination of immunolabelling for glutamate and GABA with the receptor immunolabelling revealed that the majority of axon terminals presynaptic to the receptor-immunoreactive synapses were enriched in glutamate immunoreactivity and were GABA-immunonegative. However, at some NR1- and GluR2/3-positive synapses, the level of glutamate immunoreactivity was low in the presynaptic terminal and, in the STN, some of them were GABA-immunopositive. It is concluded that glutamatergic transmission at individual synapses of different origins in the EP and STN is mediated by a combination ofAMPA and NMDA glutamate receptors.
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PMID:Distribution of glutamate receptor subunits at neurochemically characterized synapses in the entopeduncular nucleus and subthalamic nucleus of the rat. 967 65

The dorsal vagal complex, localized in the dorsomedial medulla, includes the nucleus tractus solitarii (NTS), the dorsal motor nucleus of the vagus nerve (DMN) and the area postrema (AP). The distribution of AMPA-preferring glutamate receptors (AMPA receptors) within this region was investigated using immunohistochemistry and antibodies recognizing either one (GluR1 or GluR4) or two (GluR2 and GluR3) AMPA receptors subunits. The distribution of GluR1 immunoreactivity showed high contrast of staining between strongly and lightly labeled areas. Labeling was intense in the AP and weak in the NTS, except for its medial and dorsalmost parts which exhibited moderate staining. Almost no GluR1 immunoreactivity was found in the DMN. GluR2/3 immunolabeling was present in the entire dorsal vagal complex. This labeling was strong in the AP, the DMN and the medial half of the NTS and moderate in the lateral half of the NTS, except for the interstitial subdivision which exhibited intense staining. Labeling induced by the GluR4 antibody was very weak throughout the dorsal vagal complex. Ultrastructural examination showed that GluR1 and GluR2/3 immunoreactivity was localized in neuronal cell bodies and dendrites. No labeled axon terminal or glial cell body was found. Immunoperoxidase staining in labeled cell bodies and dendrites was associated with intracellular organelles (microtubules, mitochondria, cisternae of the endoplasmic reticulum,.) and/or parts of the plasma membrane. Plasma membrane labeling was often associated with asymmetrical synaptic differentiations. No labeled symmetrical synapse was found using either GluR1 or GluR2/3 antibody. The present results show that AMPA receptors have a widespread distribution in neuronal perikarya and dendrites of the rat dorsal vagal complex. They suggest differences in subunit composition between AMPA receptors localized in the NTS, the DMN and the AP. Ultrastructural data are consistent with the fact that AMPA receptors associated with the plasma membrane are mostly synaptic receptors. However, they also suggest the existence of a large intracellular pool of receptor subunits in neuronal soma and dendrites.
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PMID:Distribution of AMPA receptor subunits GluR1-4 in the dorsal vagal complex of the rat: a light and electron microscope immunocytochemical study. 1045 72

In the present investigation, we address the question of whether the expression of GluR2-R4 subunits mRNAs and GluR2 and GluR4 subunits protein of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-selective glutamate receptors are modulated in the vestibular nuclei following unilateral labyrinthectomy. Specific GluR2-R4 radioactive oligonucleotides were used to probe sections of rat vestibular nuclei according to in situ hybridization methods. The signal was detected by means of film or emulsion photography. GluR2 and GluR4 subunit expression were also measured in control and operated rats by use of specific monoclonal GluR2 and GluR4 antibodies. Animals were killed at different stages following the lesion: 1, 3 or 8 days for the in situ hybridization study and 4 and 8 days for the immunohistochemical study. In normal animals, several brainstem regions including the lateral, medial, superior and inferior vestibular nuclei expressed all the GluR2, GluR3 and GluR4 subunit mRNAs. Moreover, numerous vestibular nuclei neurons are endowed with AMPA receptors containing the GluR2 and the GluR4 subunits. In unilaterally labyrinthectomized rats, no asymmetry could be detected on autoradiographs between the two medial vestibular nuclei probed with the GluR2 and the GluR4 oligonucleotide probes regardless of the delay following the lesion. However, compared to control, a bilateral decrease (-22%) in GluR3 gene expression was observed in the medial vestibular nuclei 3 days after the lesion followed by a return to normal at day 8 post-lesion. No significant asymmetrical changes in the density of GluR2- and GluR4-immunopositive cells could be detected between the intact and deafferented sides in any part of the vestibular nuclear complex and at any times (day 4 or day 8) following the lesion. Our data show that the removal of glutamatergic vestibular input induced an absence of modulation of GluR2 and GluR4 gene and subunits expression. This demonstrates that GluR2 and GluR4 expression do not play a role in the recovery of the resting discharge of the deafferented medial vestibular nuclei neurons and consequently in the functional restoration of the static postural and oculomotor deficits. The functional role of the slight and bilateral GluR3 mRNA decrease in the vestibular nuclei remains to be elucidated.
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PMID:GluR2-R4 AMPA subunit study in rat vestibular nuclei after unilateral labyrinthectomy: an in situ and immunohistochemical study. 1195 22

Input-dependent left-right asymmetry of NMDA receptor epsilon2 (NR2B) subunit allocation was discovered in hippocampal Schaffer collateral (Sch) and commissural fiber pyramidal cell synapses (Kawakami et al., 2003). To investigate whether this asymmetrical epsilon2 allocation is also related to the types of the postsynaptic cells, we compared postembedding immunogold labeling for epsilon2 in left and right Sch synapses on pyramidal cells and interneurons. To facilitate the detection of epsilon2 density difference, we used epsilon1 (NR2A) knock-out (KO) mice, which have a simplified NMDA receptor subunit composition. The labeling density for epsilon2 but not zeta1 (NR1) and subtype 2/3 glutamate receptor (GluR2/3) in Sch-CA1 pyramidal cell synapses was significantly different between the left and right hippocampus with opposite directions in strata oriens and radiatum; the left to right ratio of epsilon2 labeling density was 1:1.50 in stratum oriens and 1.44:1 in stratum radiatum. No significant difference, however, was detected in CA1 stratum radiatum between the left and right Sch-GluR4-positive (mostly parvalbumin-positive) and Sch-GluR4-negative interneuron synapses. Consistent with the anatomical asymmetry, the amplitude ratio of NMDA EPSCs to non-NMDA EPSCs in pyramidal cells was approximately two times larger in right than left stratum radiatum and vice versa in stratum oriens of epsilon1 KO mice. Moreover, the amplitude of long-term potentiation in the Sch-CA1 synapses of left stratum radiatum was significantly larger than that in the right corresponding synapses. These results indicate that the asymmetry of epsilon2 distribution is target cell specific, resulting in the left-right difference in NMDA receptor content and plasticity in Sch-CA1 pyramidal cell synapses in epsilon1 KO mice.
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PMID:Target-cell-specific left-right asymmetry of NMDA receptor content in schaffer collateral synapses in epsilon1/NR2A knock-out mice. 1620 81

AMPA receptors (AMPA-Rs) are formed as heterotetrameric combinations of subunits known as GluR1-GluR4. The calcium permeability of AMPA-Rs is controlled by the identity of the amino-acid side chain contributed by each subunit at a key position in the conductance pathway, which can be either a glutamine (Q) or an arginine (R). Tetramers assembled only from Q-containing subunits are calcium permeable. In contrast, tetramers that incorporate R-containing subunits are calcium impermeable. Both forms play key roles in physiological and pathophysiological processes in the central nervous system. Here, using electron microscopy, we present the first quaternary structure of a calcium-permeable Q-homomeric AMPA-R. The receptor is elongated, with overall 2-fold symmetry and a large central vestibule. It is thus similar to the structure previously reported for an AMPA-R assembled exclusively from R-subunits. Both structures differ from those reported for brain-derived but urea-washed "native" AMPA-Rs, which exhibited multiple asymmetrical conformations. However, even transient exposure of our Q-homomeric AMPA-Rs to urea significantly attenuates the binding of a conformationally specific antibody. As a result, we propose a model in which all AMPA-Rs share a 2-fold symmetrical structure and in which subunit-dependent differences in assembly, trafficking, and electrophysiology are mediated within the framework of fundamentally similar quaternary conformations.
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PMID:The quaternary structure of a calcium-permeable AMPA receptor: conservation of shape and symmetry across functionally distinct subunit assemblies. 1865 86