GLRA2 Membrane Protein Introduction

Introduction of GLRA2

Glycine receptor subunit alpha-2 (GLRA2) is a protein that in humans is encoded by the GLRA2 gene. Glycine receptors (GlyR) are members of the cys-loop family of ligand-gated ion channels, responsible for mediating the inhibitory effects of glycine. They are widely distributed throughout the CNS, particularly within the hippocampus, spinal cord, and brain stem. The glycine receptor consists of two subunits, alpha, and beta, and acts as a pentamer. The protein encoded by this gene is an alpha subunit and can bind strychnine. Several transcript variants encoding different isoforms have been found for this gene.

Glycine receptors (GlyRs) are homomeric or heteromeric ligand-gated chloride channels formed respectively by α subunits (α1-α4) or by a combination of α and β subunits. GlyR subunits display regional and temporal specificities in their patterns of expression. The mRNA of GlyR α1 and GlyR α3 can only be detected postnatally, with strong expression in the spinal cord; GlyR α4 transcripts are very weakly expressed in the mammalian central nervous system (CNS), while high levels of β subunit mRNA are widely distributed throughout the embryonic and adult CNS. In contrast, transcripts of GlyR α2 are found throughout the CNS during development and the expression markedly decreased after birth. Fetal GlyRs are predominantly α2-homomers.

Function of GLRA2 Membrane Protein

Glycine receptors (GlyR) are ligand-gated chloride channels, which mediate fast inhibitory transmission in the vertebrate CNS. The disruption of glycinergic transmission through inherited mutations can cause panic disease in humans. Many startle mutations that are in GlyRs provide useful clues to the function of the channel domains. The opening of channel is triggered by extracellular glycine or taurine and beta-alanine. The α2-glycine receptors play a role in the down-regulation of neuronal excitability and contribute to the generation of inhibitory postsynaptic currents. The α2-glycine receptors (GlyRs) play important roles during early central nervous system development. Among the related pathways of GLRA2 are dag and ip3 signaling peptide and ligand-binding receptors. Gene Ontology annotations associated with this gene include extracellularly glycine-gated chloride channel activity and extracellular ligand-gated ion channel activity.

Fig.1 Glycine receptor α2 subunit activation promotes cortical interneuron migration. (Avila, 2013)

Application of GLRA2 Membrane Protein in Literature

1. Lin M.S., et al. α2-glycine receptors modulate adult hippocampal neurogenesis and spatial memory. Dev Neurobiol. 2017, 77(12): 1430-1441. PubMed ID: 29057625
   
   

   The study reveals the neurodevelopmental roles for α2-GlyRs in the adult brain, which may be clinically relevant.

2. McCracken L.M., et al. Glycine receptor α3 and α2 subunits mediate tonic and exogenous agonist-induced currents in forebrain. Proc Natl Acad Sci U S A. 2017, 114(34): E7179-E7186. PubMed ID: 28784756
   
   

   The article reports that glycine receptor α3 and α2 play roles in the regulation of neuronal excitability in the forebrain. Functional α2 and α3 glycine receptors are present in various regions of the forebrain.

3. Schaefermeier P., et al. Hippocampal Characteristics and Invariant Sequence Elements Distribution of GLRA2 and GLRA3 C-to-U Editing. Mol Syndromol. 2017, 8(2): 85-92. PubMed ID: 28611548
   
   

   The article reports the distribution of hippocampal features and invariant sequence elements edited by GLRA2 and GLRA3 C-to-U.

4. Zhang Y., et al. Structure-Function Analysis of the GlyR α2 Subunit Autism Mutation p.R323L Reveals a Gain-of-Function. Front Mol Neurosci. 2017, 10: 158. PubMed ID: 28588452
   
   

   Authors in this group find that GlyR α2R323L exhibits reduced glycine sensitivity, but significantly increased inhibitory postsynaptic current (IPSC) rise and decay times. The GlyR α2 p.R323L mutation results in an overall gain of function.

5. Zhang C., et al. GlyRα2, not GlyRα3, modulates the receptive field surround of OFF retinal ganglion cells. Vis Neurosci. 2015, 32: E026. PubMed ID: 26923349
   
   

   Authors in this group investigate the possible role of GlyRα2 in modulating the receptive field surround of OFF retinal ganglion cells. The data suggest that GlyRα2 modulates the OFF RGC RF center and surround independently.

GLRA2 Preparation Options

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Reference

1. Avila A, et al. (2013). Glycine receptor α2 subunit activation promotes cortical interneuron migration. Cell Rep. 4(4): 738-50.

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