GRIA2 Membrane Protein Introduction

Introduction of GRIA2

Glutamate ionotropic receptor AMPA type subunit 2, also known as ionotropic glutamate receptor 2, is a protein that in humans is encoded by the GRIA2 (or GLUR2) gene. Glutamate receptor 2 is a member of the glutamate receptor family, which are the major excitatory neurotransmitter receptors in the mammalian brain. These receptors are heteromeric protein complexes with multiple subunits. Each of them has transmembrane regions, and all are arranged to form a ligand-gated ion channel. Glutamate receptors are activated in different normal neurophysiologic processes and the classification of them is based on their activation by different pharmacologic agonists. Glutamate receptor 2 belongs to a family of glutamate receptors that are sensitive to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), and function as ligand-activated cation channels. Each member (GRIA 1-4) includes flip and flop isoforms generated by alternative RNA splicing. Human and animal studies suggest that pre-mRNA editing is essential for brain function, and defective GRIA2 RNA editing at the Q/R site may be relevant to amyotrophic lateral sclerosis (ALS) etiology. Alternative splicing, resulting in transcript variants encoding different isoforms, has been noted for this gene, which includes the generation of flip and flop isoforms that vary in their signal transduction properties.

Function of GRIA2 Membrane Protein

A series of human and animal studies have determined that RNA editing of the Q/R site in GluR2 pre-mRNA is required for normal brain function. Defective editing is associated with several conditions such as amyotrophic lateral sclerosis (ALS). In these cases, motor neurons degenerate leads to eventual paralysis and respiratory failure. It is known that glutamate excitotoxicity contributes to the spread of the sporadic condition. Glutamate levels are increased up 40%, suggesting that activation of glutamate receptors may be responsible for increased Ca influx and then neuronal death. As editing occurs only in spinal motor neurons and not in upper spinal neurons, Q/R editing is not the only mechanism involved. Editing at the Q/R site is also found to be reduced in some human brain tumors. The decrease of ADAR2 expression is considered to be associated with epileptic seizures in malignant glioma.

Fig.1 Structure of the GRIA2 protein.

Application of GRIA2 Membrane Protein in Literature

1. Cabrera-Pastor A., et al. Chronic hyperammonemia alters in opposite ways membrane expression of GluA1 and GluA2 AMPA receptor subunits in cerebellum. Molecular mechanisms involved. Biochim Biophys Acta. 2018, 1864(1): 286-295. PubMed ID: 29107806
   
   

   This article reveals that chronic hyperammonemia alters the membrane expression of GluA1 and GluA2 AMPA receptor subunits in cerebellum in opposite ways, which may result in cognitive and motor alterations in hyperammonemia and hepatic encephalopathy.

2. Ancona Esselmann S.G., et al. Synaptic homeostasis requires the membrane-proximal carboxy tail of GluA2. Proc Natl Acad Sci U S A. 2017, 114(50): 13266-13271. PubMed ID: 29180434
   
   

   Authors in this group demonstrate that a single amino acid within the membrane-proximal region of the GluA2 cytoplasmic tail plays an important role in synaptic homeostasis.

3. Lorgen JØ., et al. PICK1 facilitates lasting reduction in GluA2 concentration in the hippocampus during chronic epilepsy. Epilepsy Res. 2017, 137: 25-32. PubMed ID: 28888867
   
   

   The article indicates that the reduction in PICK1 concentration may be an independent contributor to the observed GluA2 reduction, which may possibly be an adaptive mechanism, serving to prevent further loss of GluA2 from the synapses.

4. Ellis A.S., et al. Disruption of GluA2 phosphorylation potentiates stress responsivity. Behav Brain Res. 2017, 333: 83-89. PubMed ID: 28668281
   
   

   The article reveals that disrupting GluA2 phosphorylation results in increased responsivity to acute stress after cocaine exposure and increased vulnerability to chronic stress.

5. Han Y., et al. Functional Roles of the Edited Isoform of GluA2 in GluA2-Containing AMPA Receptor Channels. Biochemistry. 2017, 56(11): 1620-1631. PubMed ID: 28244309
   
   

   This article reports that GluA2R is the dominating isoform that shapes the overall functional properties of the GluA2R-containing channels and it is most likely binds to glutamate.

GRIA2 Preparation Options

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