GRM2 Membrane Protein Introduction

Introduction of GRM2

GRM2 (mGluR2) is one of the group II metabotropic glutamate receptors (mGluRs), which are coupled to G_i/o. mGluRs belong to the family C of the G-protein coupled receptors (GPCRs) and act to modulate neuronal excitability and synaptic transmission in many brain regions. Like other mGluRs, GRM2 is composed of two main domains, including a large extracellular domain and a 7 transmembrane region. The large extracellular domain is termed the Venus Flytrap domain, which contains the glutamate-binding site. In terms of signaling pathways, GRM2 is involved in signaling pathways including inhibition of adenylyl cyclase, activation of K⁺ channels, and inhibition of Ca⁺⁺ channels.

Basic Information of GRM2
Protein Name	Metabotropic glutamate receptor 2
Gene Name	GRM2
Organism	Homo sapiens (Human)
UniProt ID	Q14416
Transmembrane Times	7
Length (aa)	872
Sequence	MGSLLALLALLLLWGAVAEGPAKKVLTLEGDLVLGGLFPVHQKGGPAEDCGPVNEHRGIQ RLEAMLFALDRINRDPHLLPGVRLGAHILDSCSKDTHALEQALDFVRASLSRGADGSRHI CPDGSYATHGDAPTAITGVIGGSYSDVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDY FARTVPPDFFQAKAMAEILRFFNWTYVSTVASEGDYGETGIEAFELEARARNICVATSEK VGRAMSRAAFEGVVRALLQKPSARVAVLFTRSEDARELLAASQRLNASFTWVASDGWGAL ESVVAGSEGAAEGAITIELASYPISDFASYFQSLDPWNNSRNPWFREFWEQRFRCSFRQR DCAAHSLRAVPFEQESKIMFVVNAVYAMAHALHNMHRALCPNTTRLCDAMRPVNGRRLYK DFVLNVKFDAPFRPADTHNEVRFDRFGDGIGRYNIFTYLRAGSGRYRYQKVGYWAEGLTL DTSLIPWASPSAGPLPASRCSEPCLQNEVKSVQPGEVCCWLCIPCQPYEYRLDEFTCADC GLGYWPNASLTGCFELPQEYIRWGDAWAVGPVTIACLGALATLFVLGVFVRHNATPVVKA SGRELCYILLGGVFLCYCMTFIFIAKPSTAVCTLRRLGLGTAFSVCYSALLTKTNRIARI FGGAREGAQRPRFISPASQVAICLALISGQLLIVVAWLVVEAPGTGKETAPERREVVTLR CNHRDASMLGSLAYNVLLIALCTLYAFKTRKCPENFNEAKFIGFTMYTTCIIWLAFLPIF YVTSSDYRVQTTTMCVSVSLSGSVVLGCLFAPKLHIILFQPQKNVVSHRAPTSRFGSAAA RASSSLGQGSGSQFVPTVCNGREVVDSTTSSL

Functions of GRM2 Membrane Protein

In humans, GRM2 is only expressed in the brain including neurons and astrocytes. GRM2 is predominantly localized at the periphery of the presynaptic terminal. GRM2-deficient mice had been used to study the functions of this receptor. These animals showed normal regulation of basal synaptic transmission and long-term potentiation (LTD) but were severely impaired in terms of LTD induced by low-frequency stimulation at this synapse. In other studies, GRM2 activation was suggested to result in cognitive impairment and had been implicated in addiction to drugs of abuse. As a result, antagonists of this receptor have been considered promising candidates for the treatment of anxiety and other brain disorders.

GRM2 Membrane Protein Introduction

Applications of GRM2 Membrane Protein in Literature

Cross A. J., et al. Metabotropic glutamate receptors 2 and 3 as targets for treating nicotine addiction. Biol Psychiatry. 2017. PubMed ID: 29301614

This article demonstrated that mGluR2/3 was a promising target in the search for smoking cessation medication.
Xing B., et al. Juvenile treatment with mGluR2/3 agonist prevents schizophrenia-like phenotypes in adult by acting through GSK3β. Neuropharmacology. 2018. PubMed ID: 29793154

This article investigated the mechanisms for mGluR2/3 agonists against N-methyl-D-aspartate receptor (NMDAR) hypofunction. Results showed that early interventions with mGluR2/3 agonists prevented Schizophrenia-like electrophysiological, morphological, and cognitive deficits in adults via restoring NMDAR signaling during a critical postnatal period.
Baharlouei N., et al. Microinjection of the mGluR2/3 agonist, LY379268, into the nucleus accumbens attenuates extinction latencies and the reinstatement of morphine-induced conditioned place preference in rats. Behavioural Pharmacology. 2018: 1. PubMed ID: 29462112

This article investigated the effects of mGluR2/3 agonist, LY379268, on the extinction and reinstatement of morphine-induced conditioning place preference. LY379268 agonist seemed to be a potential role in the drug-seeking behaviors.
Chandrasekaran K., et al. mGluR2/3 activation of the SIRT1 axis preserves mitochondrial function in diabetic neuropathy. Annals of Clinical & Translational Neurology. 2017, 4(12): 844. PubMed ID: 29296613

This article demonstrated that a selective mGluR2/3 agonist was effective in reducing the severity of diabetic neuropathy.
Gjørlund M. D., et al. Soluble ectodomain of neuroligin 1 decreases synaptic activity by activating metabotropic glutamate receptor 2. Frontiers in Molecular Neuroscience. 2017, 10:116. PubMed ID: 28515678

This article demonstrated that the soluble extracellular domain of neuroligin 1 functionally interacted with mGluR2 and thereby decreasing synaptic strength.

GRM2 Preparation Options

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