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)

The mitral cell of the olfactory bulb is the primary relay neuron that transmits information from the olfactory receptors to the rest of the brain. This excitatory neuron releases glutamate from presynaptic dendrites and axon terminals. All rat mitral cells studied showed strong, selective, and widespread metabotropic glutamate receptor mGluR1 alpha immunoreactivity on the presynaptic membrane of dendrites, often at the synaptic vesicle release site, when examined with light and electron microscopy. The finding of glutamate receptors on mitral cell secondary dendrites supports the conclusion that not all dendritic membrane with glutamate receptors necessarily have gray type I asymmetrical synaptic specializations. In contrast, the metabotropic glutamate receptor mGluR5 was not found in mitral cells but was expressed by granule cells and astrocytes around mitral dendrites. Both mGluR1 alpha and mGluR5 were expressed early in development, with strong immunostaining present by postnatal day 1. MGluR1 alpha staining at birth mirrored the adult staining pattern. MGluR5 staining at birth showed different patterns of immunostaining than that found in the adult, particularly in the external plexiform layer. In vitro olfactory bulb neurons and their dendrites from embryonic day (E) 18 olfactory bulbs responded to t-ACPD and quisqualate, selective and nonselective metabotropic glutamate receptor agonists, and to several ionotropic glutamate agonists with increases in intracellular Ca2+ as studied with fura-2 digital imaging. These data indicate that the receptors were functionally active at an early stage of development. Application of the glutamate receptor blockers d-2-amino-5-phosphonovalerate (AP5) and 6-cyano-7-nitroquinoxaline (CNQX) to E17 olfactory bulb neurons after only 4 days in vitro resulted in a dramatic decrease in Ca2+ levels in 70% of 128 cells tested, suggesting that embryonic neurons after a short time in vitro can actively secrete glutamate. The presence of glutamate receptors on the long mitral cell dendrite suggests that it would be able to respond to release of its own excitatory transmitter, probably at an early stage of development. In the probable absence of other excitatory input to the secondary mitral dendrites, it would be the only excitatory "input." This autoexcitatory response would be modulated by release of GABA from olfactory interneurons occurring milliseconds after glutamate release induced by olfactory nerve activation. This novel type of neuronal microcircuitry would potentially amplify signal transmission and current spread along the long mitral dendrites and could play an important role in lateral inhibition of olfactory neurons.
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PMID:Presynaptic metabotropic glutamate receptors in adult and developing neurons: autoexcitation in the olfactory bulb. 749 28

The cellular and subcellular distribution of the mGluR5a metabotropic glutamate receptor was studied in the spinal cord of the rat using an antibody raised against a mGluR5a-specific carboxy-terminal peptide. Strong mGluR5a-immunoreactivity (mGluR5a-ir) was found in the laminae I-II of the dorsal horn, which gradually decreased towards the deeper layers. At the electron microscopical level, mGluR5a-ir was present exclusively in neuronal somata and dendrites. Immunometal labelling revealed that mGluR5a-ir is concentrated at the periphery of postsynaptic densities of asymmetrical synapses or localized extrasynaptically at dendritic and somatic membranes. The mGluR5a-immunoreactive dendritic profiles were often targeted by synaptic boutons with the morphological characteristics of C-fibre terminals. These observations provide evidence for mGluR5a being involved in the nociceptive transmission at the dorsal horn.
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PMID:Cellular and subcellular localization of the mGluR5a metabotropic glutamate receptor in rat spinal cord. 770 17

A trpE-fusion protein containing a C-terminal sequence of a rat metabotropic glutamate receptor, mGluR5, was used to produce an antibody. On immunoblot, the antibody specifically reacted with mGluR5 expressed in mammalian cells and rat brain. Immunohistochemical analysis revealed intense mGluR5-like immunoreactivity (LI) in the olfactory bulb, anterior olfactory nuclei, olfactory tubercle, cerebral cortex, hippocampus, lateral septum, striatum, nucleus accumbens, inferior colliculus, and spinal trigeminal nuclei. The distribution pattern of mGluR5-LI corresponds very well with that of mGluR5 mRNA. Electron microscope analysis of the striatum revealed dense accumulation of immunoreaction products in dendrites which were often provided with asymmetrical synapses. These results suggest that mGluR5 is predominantly located in postsynaptic elements.
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PMID:Immunohistochemical localization of a metabotropic glutamate receptor, mGluR5, in the rat brain. 829 33

The metabotropic glutamate receptor mGluR5 is a G-protein coupled receptor that plays a key role in release of Ca2+ from internal stores via inositol triphosphate mobilization. Western and Northern blot analyses revealed a greatly enhanced expression of mGluR5 in rats during early stages of hypothalamic development compared with the adult. This enhanced developmental expression provides an explanation for the dramatic physiological response of developing neurons to metabotropic glutamate receptor activation and supports the argument that metabotropic glutamate receptors may play an important role in hypothalamic development. During development, expression of the mGluR5 gene was reduced, not only in the hypothalamus but also in other regions of the brain. A differential decrease in mGluR5 protein was found in different brain regions with Western blot analysis. The hypothalamus showed a sixfold decrease in mGluR5 with development, whereas the cortex showed only a threefold decrease. Immunocytochemistry with an affinity-purified antibody against a peptide deduced from the cloned mGluR5 gene revealed selective expression in some regions in the adult hypothalamus. In the adult and developing (postnatal day 10) brain, immunoreactive neurons were found in the suprachiasmatic nucleus, preoptic area, lateral hypothalamus, and mammillary region, areas where the related metabotropic glutamate receptor mGluR1 is also found. In contrast, the ventromedial nucleus, an area critically involved in the regulation of food intake and metabolic balances, showed strong mGluR5 immunoreactivity but no mGluR1 immunoreactivity. Little or no mGluR5 staining was found in the neurosecretory neurons of the paraventricular, supraoptic, and arcuate nuclei. Ultrastructurally, mGluR5 was associated with the cytoplasmic face of the plasmalemma on hypothalamic dendrites, dendritic spines, and neuronal perikarya in the adult. The strongest immunoreactivity was found in patches on the membrane, sometimes associated with the postsynaptic side of synapses and sometimes associated with nonsynaptic dendritic or perikaryal membrane. Intense immunostaining was found on some astrocyte processes surrounding synaptic complexes containing asymmetrical synapses. These astrocytes would be in an ideal position to receive excitatory signals from glutamatergic axons. Unlike the punctate appearance of immunolabeling on neuronal membranes, astrocytes showed continuous staining along the plasma membrane.
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PMID:Metabotropic glutamate receptor mGluR5 subcellular distribution and developmental expression in hypothalamus. 857 26

Neurotransmission in the hippocampus is modulated variously through presynaptic metabotropic glutamate receptors (mGluRs). To establish the precise localization of presynaptic mGluRs in the rat hippocampus, we used subtype-specific antibodies for eight mGluRs (mGluR1-mGluR8) for immunohistochemistry combined with lesioning of the three major hippocampal pathways: the perforant path, mossy fiber, and Schaffer collateral. Immunoreactivity for group II (mGluR2) and group III (mGluR4a, mGluR7a, mGluR7b, and mGluR8) mGluRs was predominantly localized to presynaptic elements, whereas that for group I mGluRs (mGluR1 and mGluR5) was localized to postsynaptic elements. The medial perforant path was strongly immunoreactive for mGluR2 and mGluR7a throughout the hippocampus, and the lateral perforant path was prominently immunoreactive for mGluR8 in the dentate gyrus and CA3 area. The mossy fiber was labeled for mGluR2, mGluR7a, and mGluR7b, whereas the Schaffer collateral was labeled only for mGluR7a. Electron microscopy further revealed the spatial segregation of group II and group III mGluRs within presynaptic elements. Immunolabeling for the group III receptors was predominantly observed in presynaptic active zones of asymmetrical and symmetrical synapses, whereas that for the group II receptor (mGluR2) was found in preterminal rather than terminal portions of axons. Target cell-specific segregation of receptors, first reported for mGluR7a (Shigemoto et al,., 1996), was also apparent for the other group III mGluRs, suggesting that transmitter release is differentially regulated by 2-amino-4-phosphonobutyrate-sensitive mGluRs in individual synapses on single axons according to the identity of postsynaptic neurons.
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PMID:Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus. 929 96

The distributions of two alternative splicing variants of metabotropic glutamate receptor mGluR7, mGluR7a and mGluR7b, were examined immunohistochemically in the rat and mouse by using variant-specific antibodies raised against C-terminal portions of rat mGluR7a and human mGluR7b. Many regions throughout the central nervous system (CNS) showed mGluR7-like immunoreactivities (LI). The distribution patterns of mGluR7-LI in the rat were substantially the same as those in the mouse, although some species differences were observed in a few regions. Intense mGluR7a-LI was seen in the main and accessory olfactory bulbs, anterior olfactory nucleus, islands of Calleja, superficial layers of the olfactory tubercle, piriform cortex and entorhinal cortex, periamygdaloid cortex, amygdalohippocampal area, hippocampus, layer I of the neocortical regions, globus pallidus, superficial layers of the superior colliculus, locus coeruleus, and superficial layers of the medullary and spinal dorsal horns. The distribution of mGluR7b was more restricted. It was intense in the islands of Calleja, substantia innominata, hippocampus, ventral pallidum, and globus pallidus. The medial habenular nucleus also showed intense mGluR7a-LI in the rat but not in the mouse. For both mGluR7a- and mGluR7b-LI, localization in the active zones of presynaptic axon terminals was confirmed electron microscopically at synapses of both the asymmetrical and symmetrical types. It is noteworthy that mGluR7a-LI is seen preferentially in relay nuclei of the sensory pathways and that both mGluR7a- and mGluR7b-LI are observed not only in presumed glutamatergic axon terminals, but also in non-glutamatergic axon terminals including presumed inhibitory ones. Thus, mGluR7 may play roles not only as an autoreceptor in glutamatergic axon terminals, but also as a presynaptic heteroreceptor in non-glutamatergic axon terminals in various CNS regions.
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PMID:Immunohistochemical localization of metabotropic glutamate receptors, mGluR7a and mGluR7b, in the central nervous system of the adult rat and mouse: a light and electron microscopic study. 954 54

High resolution immunoelectron microscopy was used to study subcellular localization patterns of three metabotropic glutamate receptor subtypes (mGluR1alpha, mGluR5, and mGluR2/3) during postnatal development of mouse ventral posterior (VP) thalamic nucleus. Immunoreactivity for all three mGluRs was detected from birth (postnatal day 0, P0), but mGluR1alpha showed dramatic changes in localization with age. In the first postnatal week, mGluR1alpha immunoreactivity was mainly found in proximal dendrites and somata and not usually associated with synaptic contacts. From the second postnatal week, it became concentrated in distal dendrites and preferentially associated with corticothalamic (RS) synapses. mGluR5 immunoreactivity was weaker than mGluR1alpha immunoreactivity at all postnatal ages and showed a similar change in subcellular distribution to that of mGluR1alpha. It was also localized in astrocytic processes. mGluR2/3 immunoreactivity was mainly localized in astrocytic processes surrounding neuronal somata and synapses and this pattern was consistently maintained through all postnatal ages. A small number of presynaptic axon terminals were labeled for mGluR2/3 immunoreactivity and formed asymmetrical synapses. This study demonstrates that Group I mGluR proteins (mGluR1alpha and mGluR5) become redistributed in association with the development of corticothalamic function as demonstrated physiologically, whereas Group II mGluR proteins (mGluR2/3) are mainly associated with neuroglia.
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PMID:Changes in subcellular localization of metabotropic glutamate receptor subtypes during postnatal development of mouse thalamus. 961 99

Neurons in the rat cerebral cortex are enriched in group I metabotropic glutamate receptor (mGluR) subtypes and respond to their activation during development. To understand better the mechanisms by which mGluR1 and mGluR5 mediate these effects, the goal of this study was to elucidate the expression pattern and to determine the cellular and the precise subcellular localization of these two receptor subtypes in the rat neocortex and hippocampus during late prenatal and postnatal development. At the light microscopic level, mGluR1alpha and mGluR5 were first detected in the cerebral cortex with different expression levels at embryonic day E18. Thus, mGluR5 had a moderate expression, whereas mGluR1alpha was detected as a diffuse and weak labeling. mGluR5 was localized in some Cajal- Retzius cells as well as in other cell types, such as pioneer neurons of the marginal zone. During postnatal development, the distribution of the receptors dramatically changed. From P0 to around P10, mGluR1alpha was localized in identified, transient Cajal-Retzius cells of neocortex and hippocampus, until these cells disappear. In addition, a population of interneurons localized the receptor from the second/third postnatal week. In contrast, mGluR5 was localized mainly in pyramidal cells and in some interneurons, with a neuropilar staining throughout the cerebral cortex. At the electron microscopic level, the immunoreactivity for both group I mGluR subtypes was expressed postsynaptically. Using immunogold methods, mGluR1alpha and mGluR5 immunoreactivities were found throughout postnatal development at the edge of postsynaptic specialization of asymmetrical synapses. These results show that the two group I mGluRs have a differential expression pattern in neocortex and hippocampus that may suggest roles for the receptors in the early processing of cortical information and in the control of cortical developmental events.
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PMID:Differential distribution of group I metabotropic glutamate receptors during rat cortical development. 1200 62

Upon activation of receptors coupled to the Gq subclass of G proteins, phospholipase C (PLC)beta hydrolyses membrane phospholipid to yield a pair of second messengers, inositol 1,4,5-trisphosphate and 1,2-diacylglycerol. Of four PLCbeta isoforms, PLCbeta1 is transcribed predominantly in the telencephalon and its gene inactivation in mice impairs metabotropic glutamate receptor- and muscarinic acetylcholine receptor-dependent hippocampal oscillations, endocannabinoid production in the hippocampus and barrel formation in the somatosensory cortex. Here we examined cellular and subcellular distributions of PLCbeta1 in adult mouse brains. In the telencephalon, high levels of PLCbeta1 were observed in principal neurons, including pyramidal cells in the cortex and hippocampus, granule cells and mossy cells in the dentate gyrus, and medium spiny neurons in the caudate-putamen, whereas most interneurons had low levels of or were negative for PLCbeta1 and, instead, expressed PLCbeta4. By immunofluorescence, tiny clusters of PLCbeta1 were distributed in somatodendritic compartments of principal neurons and positioned close to those of metabotropic glutamate receptor 5, muscarinic acetylcholine receptor M1 and diacylglycerol lipase-alpha, respectively. Immunoelectron microscopy revealed that PLCbeta1 was often associated with the smooth endoplasmic reticulum, cell membrane or postsynaptic density. In particular, it was highly accumulated at the perisynapse of dendritic spines forming asymmetrical synapses. In the cerebellum, PLCbeta1 was generally low but was enriched in axons and dendrites of basket cells. These results suggest that PLCbeta1 is the key effector in telencephalic principal neurons and cerebellar interneurons. Furthermore, the well-orchestrated molecular arrangement appears to be the anatomical basis for the specificity, efficiency and convergence of the neuronal phosphoinositide signaling system.
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PMID:Predominant expression of phospholipase Cbeta1 in telencephalic principal neurons and cerebellar interneurons, and its close association with related signaling molecules in somatodendritic neuronal elements. 1897 90

The gamma-aminobutyric acid type B receptor (GABA(B)R), one of the family C G-protein-coupled receptor members, exists as a heterodimer comprised of subunits GB1 and GB2. To clarify the ligand-induced activation mechanism of the GABA(B)R, each subunit was fused with either Cerulean or enhanced yellow fluorescent protein at its intracellular loop, and fluorescence resonance energy transfer (FRET) changes upon agonist application were monitored. As a result, FRET decreases were observed between GB1a loop 2 and GB2 loop 2 and between GB1a loop 2 and GB2 loop 1, suggesting the dissociation of intracellular domains during the receptor activation. Both intersubunit FRET pairs were expected to faithfully capture the activation of the original receptor as their pharmacological properties were highly similar to that of the wild-type receptor. However, the intrasubunit data suggest that the receptor activation does not involve major structural changes within the transmembrane domain of each subunit. By combining the results obtained from two different levels, it was concluded that the GABA(B)R activation by agonist is associated with an asymmetrical intersubunit rearrangement of GB1a and GB2 on the membrane. This type of activation mode, an intersubunit rearrangement without apparent intrahelical structural changes, appears commonly shared by the GABA(B)R and the metabotropic glutamate receptor 1alpha, another family C G-protein-coupled receptor previously studied by our group. Nevertheless, the directions of intracellular domain movements and its asymmetry observed here highlight the qualitative difference between the two receptors.
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PMID:Ligand-induced rearrangements of the GABA(B) receptor revealed by fluorescence resonance energy transfer. 2012 19


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