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Metabotropic Glutamate - Crossref

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Last Updated: 08 May 2022

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Localization and function of group III metabotropic glutamate receptors in rat pancreatic islets

According to a RT-PCR analysis, rats islets secretly have the mGlu8 receptor subtype. We established that -cells have a glutamatergic phenotype by demonstrating the immunoactivities of both glutamate and the vesicular glutamate transporter 2 in these cells. MGlu8 expression by glutamatergic cells also shows that mGlu8 may act as an autoreceptor to control glutamate release. Because excess glucagon secretion causes postprandial hyperglycemia in patients with type 2 diabetes, patients with type 2 diabetes, group III mGlu receptor agonists may be of use in the treatment of these patients.

Source link: https://doi.org/10.1152/ajpendo.00460.2001


Conformational fingerprinting of allosteric modulators in metabotropic glutamate receptor 2

Conformational coupling between the orthosteric ligand binding site and the G protein binding site is involved in conformational coupling. Allosteric modulators are therapeutics that bind to factors other than the orthosteric ligand binding site and alter this allosteric activation process. Here, we developed FRET sensors to measure receptor modulation at each of Metabotropic glutamate receptor 2's three structural domains. A NAM increases the occupancy of one of the intermediate states' homes, according to a single-molecule FRET study, while a PAM raises the occupancy of the active state.

Source link: https://doi.org/10.1101/2022.04.27.489706


Ca 2+ activity at GABA B receptors constitutively promotes metabotropic glutamate signaling in the absence of GABA

GABA B Rs are concentrated in various neurons and are concentrated at excitatory synapses in excitatory synapses. In cerebellar Purkinje cells, GABA B R's association with extracellular Ca 2+ results in a corresponding rise in the glutamate sensitivity of metabotropic glutamate receptor 1's glutamate receptor 1. GABA B R is mediated by mGluR1 sensitization in cells that are not present in GABA B R1 subunit-knockout cells, and it is clearly controlled by the GABA B R1. These results reveal that GABA B R can act as a documentclass[12pt]minimal usagepackageamsmath,usepackageamsfonts,usepackageamssymb usepackageamssymb, a gindocument that enables neuronal glutamate signaling.

Source link: https://doi.org/10.1073/pnas.0405387101


Glutamate-binding affinity of Drosophila metabotropic glutamate receptor is modulated by association with lipid rafts

Metabotropic glutamate receptors are responsible for the decline of synaptic transmission and are involved in the regulation of several CNS processes. We have recently reported the expression and purification of a mGluR from Drosophila melanogaster, a homologue of mammalian group II mGluRs. We have found that ligand binding to reconstituted DmGluRA requires the presence of ergosterol in the liposomes, according to Eroglu, C. , Cronet, P. , Panneels, V. , Beaufils, I. EMBO Rep. 3, 491-496]. Here we show that the receptor is present in various affinity states for glutamate, based on the membrane composition.

Source link: https://doi.org/10.1073/pnas.1737042100


Opposing effects of protein kinase C and protein kinase A on metabotropic glutamate receptor signaling: Selective desensitization of the inositol trisphosphate/Ca 2+ pathway by phosphorylation of the receptor-G protein-coupling domain

Protein kinase C has been reported that receptor-induced stimulation of the Ins P 3 pathway has resulted in feedback inhibition mediated by protein kinase C. PKC signaling via cAMP is selectively inhibits agonist-dependent stimulation of the Ins P 3 pathway but does not have a bearing on receptor signaling via cAMP. Likewise, we show that PKC's selectiveness in receptor signaling stems from the phosphorylation of a threonine fragment embedded in the receptor's G protein-interacting domain. Modification at Thr 695 selectively disrupts mGluR1-G q/11 interaction without impacting signaling via G s. These findings, as well as cross-talk between different second messenger cascades, can provide insight into the ways by which selective down-regulation of a specific receptor-dependent signaling pathway can be achieved and how cross-talk between different second messenger cascades can be used to fine-tune short- and long-term receptor function.

Source link: https://doi.org/10.1073/pnas.97.11.6185


Metabotropic glutamate receptor-initiated translocation of protein kinase p90rsk to polyribosomes: A possible factor regulating synaptic protein synthesis

The p90rsk-activating kinase ERK-2 and a well-known p90rsk substrate, glycogen synthase kinase 3, are two of the polyribosome bound proteins, which regulates translation quality by eukaryotic initiation factor 2B. Thus, metabotropic glutamate receptor stimulation may result in synaptic activity-dependent translation by relocation of p90rsk to ribosomes.

Source link: https://doi.org/10.1073/pnas.95.25.15078


Modulation of the intracellular calcium concentration in photoreceptor terminals by a presynaptic metabotropic glutamate receptor

Fast excitatory neurotransmission in the central nervous system is facilitated by glutamate receptor stimulation in the ionotropic glutamate receptors. However, glutamate receptor antagonists acting on metabotropic glutamate receptors may also trigger an inhibitory reaction. The III metabotropic glutamate receptor mGluR8 is the first glutamate receptor to be discovered in mammalian retinas in terminals of photoreceptors. An increase in the intracellular calcium ion concentration in isolated photoreceptors is triggered by the production of mGluR8 by the company III mGluR agonists, l -2-amino-4-phosphonobutyrate and l -serine-O phosphate, or glutamate itself. The down-regulation of the [Ca 2+ ] i in photoreceptors by mGluR8 shows there is evidence for an inhibitory feedback loop at the photoreceptor synapse in the mammalian retina. Such a device may be used as a model for feedback inhibition in other areas of the central nervous system.

Source link: https://doi.org/10.1073/pnas.96.17.9909


Direct effects of metabotropic glutamate receptor compounds on native and recombinant N -methyl- d -aspartate receptors

Glutamate transports in the central nervous system are controlled by interaction with fast-activating ionotropic receptors and G protein-coupled metabotropic glutamate receptors. Compounds that were thought to be selective for mGluRs have been extensively used to investigate the role of these receptors in the brain. We found that several of the most commonly used mGluR compounds behave as antagonists to NMDA receptors in concentrations that are typically used to activate or block mGluRs.

Source link: https://doi.org/10.1073/pnas.95.15.8969


Involvement of unique leucine-zipper motif of PSD-Zip45 (Homer 1c/vesl-1L) in group 1 metabotropic glutamate receptor clustering

Several scaffold proteins for neurotransmitter receptor receptors have been identified as candidates for receptor targeting. The conversion of mGluR1 or mGluR5 and PSD-Zip45/Homer 1c into COS-7 cells results in mGluR clustering caused by PSD-Zip45/Homer 1c. This leucine-zipper motif of PSD-Zip45/Homer 1c in mGluR clustering also shows a significant role of this leucine-zipper motif of PSD-Zip45/Homer 1c in mGluR clustering. These findings show that the leucine zipper of subsynaptic scaffold protein is a candidate motif involved in neurotransmitter receptor clustering at the central synapse.

Source link: https://doi.org/10.1073/pnas.96.24.13801


Endogenous activation of metabotropic glutamate receptors in neocortical development causes neuronal calcium oscillations

Here, we report that developing murine cortical neurons exhibit calcium oscillations in response to the group's I metabotropic glutamate receptor's direct activation of the mGluR5 subtype. In addition, we find that spontaneous oscillatory [Ca 2+ ] i activity is blocked by antagonists of group I mGluRs, suggesting a specific role for mGluR activation in the promotion of oscillatory [Ca 2+ ] kinetics in immature cortical neurons.

Source link: https://doi.org/10.1073/pnas.96.21.12144

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions