GABRG2 Membrane Protein Introduction

Introduction of GABRG2

Gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), also known as GABA(A) receptor subunit gamma-2, is a protein that in humans is encoded by the GABRG2 gene. It belongs to the GABA receptors family which is the major inhibitory neurotransmitter in the brain and mediates neuronal inhibition by binding to GABA receptors.

Function of GABRG2 Membrane Protein

GABRG2 encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammalian brain, where it acts on GABAA receptors, ligand-gated chloride channels. This ligand-receptor binding results in the influx of chloride ions through ion channels. Studies have shown that GABRG2 is abundantly expressed in the mammalian brain and its encoded γ2 subunit is assembled into αβγ2 receptors, which are the major GABAA receptor isoforms in the brain. In particular, the γ2 subunits play a critical role in GABAA receptor trafficking and clustering at synapses. Recently, it has been reported that GABRG2 is essential for the benzodiazepine binding at the GABAA receptor and modulates the sensitivity of GABAA receptors to alcohol. What’s more, different GABRG2 mutations may result in dissimilar molecular defects due to differences in mutant protein metabolism.

Fig.1 Schematic representation of typical GABA-A receptor (GABA-AR) structure and subunit composition. (Chuang, 2018)

Application GABRG2 of Membrane Protein in Literature

1. Shen D., et al. De novo GABRG2 mutations associated with epileptic encephalopathies. Brain. 2016, 140(1):49-67. PubMed ID: 27864268
   
   

   This article further expands the GABRG2 phenotypic spectrum and supports growing evidence that defects in GABAergic neurotransmission participate in the pathogenesis of genetic epilepsies including epileptic encephalopathies.

2. Zou F., et al. Expanding the phenotypic spectrum of GABRG2 variants: a recurrent GABRG2 missense variant associated with a severe phenotype. Journal of neurogenetics. 2017, 31(1-2):30-6. PubMed ID: 28460589
   
   

   This article explores a recurrent pathogenic missense variant within the GABRG2 variant family and broadens the spectrum of associated phenotypes for GABRG2-associated disorders.

3. Kang J.Q and Macdonald R.L. Molecular pathogenic basis for GABRG2 mutations associated with a spectrum of epilepsy syndromes, from generalized absence epilepsy to dravet syndrome. JAMA Neurology. 2016, 73(8):1009-16. PubMed ID: 27367160
   
   

   This article suggests that the epilepsy phenotypic heterogeneity associated with GABRG2 mutations may be related to the extent of the reduction of GABAA receptor channel function and the differential dominant negative suppression, as well to toxicity related to the metabolism of mutant subunit proteins resulting from each mutant γ2 subunit, in addition to different genetic backgrounds.

4. Dixit A.B., et al. Mutations in GABRG2 receptor gene are not a major factor in the pathogenesis of mesial temporal lobe epilepsy in Indian population. Annals of Indian Academy of Neurology. 2016, 19(2):236. PubMed ID: 27293336
   
   

   This research indicates that GABRG2 gene may not be playing a significant role in the development of epilepsy or as a susceptibility gene in patients with MTLE in Indian population.

5. Zai C.C., et al. Association study of GABRG2 polymorphisms with suicidal behavior in schizophrenia patients with alcohol use disorder. Neuropsychobiology. 2014, 69(3):154-8. PubMed ID: 24776921
   
   

   This article suggests that GABRG2 may be involved in suicidal behavior in schizophrenia patients with alcohol dependence or abuse, but replications are required. These results may help in the discovery of novel treatments for alcoholism and/or prevention of suicide.

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Reference

1. Chuang, et al. (2018). Genetic and molecular regulation of extrasynaptic GABA-A receptors in the brain: therapeutic insights for epilepsy. Journal of Pharmacology and Experimental Therapeutics. 364(2), 180-197.

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