Cloning, Expression, and Gene Structure of a G Protein-Coupled Glutamate Receptor from Rat Brain

Houamed, Khaled M.; Kuijper, Joseph L.; Gilbert, Teresa; Haldeman, Betty A.; O׳Hara, Patrick J.; Mulvihill, Eileen R.; Almers, Wolfhard; Hagen, Frederick S.

doi:10.1126/science.1656524

Cited by 496 publications

(235 citation statements)

References 42 publications

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“…These findings opened up the possibility that glutamate, like many other neurotransmitters, activates both ligand-gated ion channels and G-protein-coupled receptors, now called metabotropic glutamate receptors (mGluRs). Since the cloning of the first mGluR in 1991 (Houamed et al 1991 ;Masu et al 1991), our knowledge on the structure, localisation and functions of this receptor family has increased substantially. Eight subtypes of mGluRs have now been cloned and subdivided into 3 major groups on the basis of sequence similarity, pharmacological properties and transduction pathways (Nakanishi, 1994 ;Pin & Duvoisin, 1995 ;Conn & Pin, 1997).…”

Section: mentioning

confidence: 99%

GABA_B and group I metabotropic glutamate receptors in the striatopallidal complex in primates

et al. 2000

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Glutamate and GABA neurotransmission is mediated through various types of ionotropic and metabotropic receptors. In this review, we summarise some of our recent findings on the subcellular and subsynaptic localisation of GABA B and group I metabotropic glutamate receptors in the striatopallidal complex of monkeys. Polyclonal antibodies that specifically recognise GABA B R1, mGluR1a and mGluR5 receptor subtypes were used for immunoperoxidase and pre-embedding immunogold techniques at the light and electron microscope levels. Both subtypes of group I mGluRs were expressed postsynaptically in striatal projection neurons and interneurons where they aggregate perisynaptically at asymmetric glutamatergic synapses and symmetric dopaminergic synaptic junctions. Moreover, they are also strongly expressed in the main body of symmetric synapses established by putative intrastriatal GABAergic terminals. In the globus pallidus, both receptor subtypes are found postsynaptically in the core of striatopallidal GABAergic synapses and perisynaptically at subthalamopallidal glutamatergic synapses. Finally, extrasynaptic labelling was commonly seen in the globus pallidus and the striatum.Moderate to intense GABA B R1 immunoreactivity was observed in the striatopallidal complex. At the electron microscope level, GABA B R1 immunostaining was commonly found in neuronal cell bodies and dendrites. Many striatal dendritic spines also displayed GABA B R1 immunoreactivity. Moreover, GABA B R1-immunoreactive axons and axon terminals were frequently encountered. In the striatum, GABA B R1-immunoreactive boutons resembled terminals of cortical origin, while in the globus pallidus, subthalamic-like terminals were labelled. Pre-embedding immunogold data showed that postsynaptic GABA B R1 receptors are concentrated at extrasynaptic sites on dendrites, spines and somata in the striatopallidal complex, perisynaptically at asymmetric synapses and in the main body of symmetric striatopallidal synapses in the GPe and GPi. Consistent with the immunoperoxidase data, immunoparticles were found in the presynaptic grid of asymmetric synapses established by cortical-and subthalamic-like glutamatergic terminals.These findings indicate that both GABA and glutamate metabotropic receptors are located to subserve various modulatory functions of the synaptic transmission in the primate striatopallidal complex. Furthermore, their pattern of localisation raises issues about their roles and mechanisms of activation in normal and pathological conditions. Because of their ' modulatory ' functions, these receptors are ideal targets for chronic drug therapies in neurodegenerative diseases such as Parkinson's disease.

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Section: mentioning

confidence: 99%

GABA_B and group I metabotropic glutamate receptors in the striatopallidal complex in primates

et al. 2000

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“…T wo commercially available affinity-purified rabbit polyclonal antibodies raised against synthetic C -terminus peptides representing different amino acid sequences of mGluR1a (PN V TYAS-V ILRDYKQSSSTL; Chemicon, Temecula, CA) and mGluR5a / b (K SSPK YDTLIIRDYTNSSSSL; Upstate Biotechnology, Lake Placid, N Y) were used in this study. In immunoblot analysis of rat brain microsomes or rabbit brain extracts, both antibodies labeled a single band with an estimated molecular weight of 145 kDA, which corresponds to that of mGluR1a and mGluR5 proteins (Houamed et al, 1991;Abe et al, 1992;Minakami et al, 1993;Testa et al, 1998).…”

Section: Immunoperoxidase Localization Of Mglur1a and Mglur5mentioning

confidence: 99%

Differential Subcellular Localization of mGluR1a and mGluR5 in the Rat and Monkey Substantia Nigra

2001

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Neurons in the rat substantia nigra (SN) are enriched in group I metabotropic glutamate receptor (mGluR) subtypes and respond to group I mGluR activation. To better understand the mechanisms by which mGluR1 and mGluR5 mediate these effects, the goal of this study was to elucidate the subsynaptic localization of these two receptor subtypes in the rat and monkey substantia nigra. At the light microscope level, neurons of the SN pars reticulata (SNr) displayed moderate to strong immunoreactivity for both mGluR1a and mGluR5 in rats and monkeys. However, mGluR1a labeling was much stronger in monkey than in rat SN pars compacta (SNc) neurons, whereas a moderate level of mGluR5 immunoreactivity was found in both species. At the electron microscope level, the immunoreactivity for both group I mGluR subtypes was primarily expressed postsynaptically, although light mGluR1a labeling was occasionally seen in axon terminals in the rat SNr. Immunogold studies revealed a striking difference in the subcellular distribution of mGluR1a and mGluR5 immunoreactivity in SNr and SNc neurons. Although the bulk of mGluR1a was attached to the plasma membrane, Ͼ80% of mGluR5 immunoreactivity was intracellular. Plasma membrane-bound immunoreactivity for group I mGluRs in both SNc and SNr neurons was mostly extrasynaptic or in the main body of symmetric, putative GABAergic synapses. On the other hand, asymmetric synapses either were nonimmunoreactive or displayed perisynaptic labeling. These data raise important questions about the trafficking, internalization, and potential functions of group I mGluRs at extrasynaptic sites or symmetric synapses in the substantia nigra. Key words: metabotropic; glutamate; receptor internalization; receptor trafficking; dopamine neurons; Parkinson's disease; immunogold methodThe substantia nigra pars reticulata (SNr) and the internal segment of the globus pallidus are the main output nuclei of the basal ganglia, whereas the SN pars compacta (SNc) is a group of dopaminergic neurons that project to the striatum. Both the SNr and SNc receive glutamatergic innervation from the subthalamic nucleus), cerebral cortex, and pedunculopontine tegmental nucleus (Wichmann and DeLong, 1998).The effects of glutamate in the CNS are mediated by activation of ionotropic and metabotropic receptors. Ionotropic receptors are ligand-gated cation channels that mediate fast excitatory neurotransmission, whereas metabotropic glutamate receptors (mGluRs) belong to a family of G-protein-coupled receptors that mediate modulatory effects of synaptic transmission by activation of a number of intracellular metabolic pathways. The family of mGluRs is subdivided into three groups (Conn and Pin, 1997). The group I mGluRs consist of mGluR1, mGluR5, and all their splice variants. These receptors are coupled to phosphoinositol hydrolysis and usually induce slow depolarization. On the other hand, group II (mGluR2,3) and group III (mGluR4,6,7,8) mGluRs are negatively coupled to adenylate cyclase and often induce presynaptic inhibition of trans...

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“…The subunits for these receptors are characterized by four transmembrane helices and are related distantly to ionotropic receptors for other neurotransmitters. In contrast, metabotropic glutamate receptors (mGluRs) contain seven putative transmembrane segments and large, globular N and C termini (Houamed et al, 1991;Masu et al, 1991;Abe et al, 1992;Tanabe et al, 1992;Nakajima et al, 1993). This family displays no sequence similarity with the extensive superfamily of heptahelical receptors for neurotransmitters, hormones, or odorants.…”

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confidence: 99%

The Taste of Monosodium Glutamate: Membrane Receptors in Taste Buds

et al. 1996

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Receptor proteins for photoreception have been studied for several decades. More recently, putative receptors for olfaction have been isolated and characterized. In contrast, no receptors for taste have been identified yet by molecular cloning. This report describes experiments aimed at identifying a receptor responsible for the taste of monosodium glutamate (MSG). Using reverse transcriptase (IV)-PCR, we found that several ionotropic glutamate receptors are present in rat lingual tissues. However, these receptors also could be detected in lingual tissue devoid of taste buds. On the other hand, RT-PCR and RNase protection assays indicated that a G-protein-coupled metabotropic glutamate receptor, mGluR4, also is expressed in lingual tissues and is limited only to taste buds. In situ hybridization demonstrated that mGluR4 is detectable in 40-70% of vallate and foliate taste buds but not in surrounding nonsensory epithelium, confirming the localization of this metabotropic receptor to gustatory cells. Expression of mGluR4 in taste buds is higher in preweaning rats compared with adult rats. This may correspond to the known higher sensitivity to the taste of MSG in juvenile rodents. Finally, behavioral studies have indicated that MSG and L-2-amino-4-phosphonobutyrate (L-AP4), a ligand for mGluR4, elicit similar tastes in rats. We conclude that mGluR4 may be a chemosensory receptor responsible, in part, for the taste of MSG.

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Cloning, Expression, and Gene Structure of a G Protein-Coupled Glutamate Receptor from Rat Brain

Cited by 496 publications

References 42 publications

GABA_B and group I metabotropic glutamate receptors in the striatopallidal complex in primates

GABA_B and group I metabotropic glutamate receptors in the striatopallidal complex in primates

Differential Subcellular Localization of mGluR1a and mGluR5 in the Rat and Monkey Substantia Nigra

The Taste of Monosodium Glutamate: Membrane Receptors in Taste Buds

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Cloning, Expression, and Gene Structure of a G Protein-Coupled Glutamate Receptor from Rat Brain

Cited by 496 publications

References 42 publications

GABAB and group I metabotropic glutamate receptors in the striatopallidal complex in primates

GABAB and group I metabotropic glutamate receptors in the striatopallidal complex in primates

Differential Subcellular Localization of mGluR1a and mGluR5 in the Rat and Monkey Substantia Nigra

The Taste of Monosodium Glutamate: Membrane Receptors in Taste Buds

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GABA_B and group I metabotropic glutamate receptors in the striatopallidal complex in primates

GABA_B and group I metabotropic glutamate receptors in the striatopallidal complex in primates