GABRA2 Membrane Protein Introduction

Introduction of GABRA2

Gamma-aminobutyric acid receptor subunit alpha-2 (GABRA2), also known as GABA(A) receptor subunit alpha-2, is encoded by the GABRA2 gene in humans. It belongs to the big GABAA receptors family which is heteropentameric, ligand-gated anion channels activated by GABA to mediate both phasic synaptic transmission and tonic extrasynaptic inhibition in the brain.

Function of GABRA2 Membrane Protein

GABA is the primary inhibitory neurotransmitter in the central nervous system and exerts its effects through binding at ionotropic (GABAA) and metabotropic (GABAB) receptors. GABRA2 is a member of GABAA receptors which are heteropentameric, ligand-gated anion channels activated by GABA to mediate both phasic synaptic transmission and tonic extrasynaptic inhibition in the brain. Studies have shown that GABRA2 is mainly expressed in brain reward circuitry including the amygdala, the ventral tegmental area, and the nucleus accumbens. It has been reported that GABRA2 potentially plays a role in the etiology of problematic drinking. What’s more, associations have been reported between GABRA2 variants and a number of alcohol-related phenotypes across developmental periods, such as adult alcohol dependence, subclinical alcohol-related risk behaviors in late adolescence and young adulthood, and problem behaviors predictive of alcohol misuse-such as conduct problems and rule-breaking behavior-during early to mid-adolescence.

Fig.1 Structure of the GABAA receptor.

Application GABRA2 of Membrane Protein in Literature

1. Orenstein N., et al. A de novo GABRA2 missense mutation in severe early-onset epileptic encephalopathy with a choreiform movement disorder. European Journal of Paediatric Neurology. 2018, 22(3):516-24. PubMed ID: 29422393
   
   

   This article suggests that a de novo mutation in GABRA2 is likely to cause autosomal dominant EOEE accompanied by a movement disorder and vision impairment.

2. Kiive E., et al. Stressful life events increase aggression and alcohol use in young carriers of the GABRA2 rs279826/rs279858 A-allele. European Neuropsychopharmacology. 2017, 27(8):816-27. PubMed ID: 28237505
   
   

   This article aims to investigate the effects of GABRA2 genotype and stressful life events on aggressive behavior, alcohol use frequency and occurrence of alcohol use disorder. It suggests that the GABRA2 genotype interacts with stress in young people with an impact on the development of alcohol use and aggressive behavior.

3. Boyd S.J., et al. Alcohol-induced stimulation mediates the effect of a GABRA2 SNP on alcohol self-administrated among alcohol-dependent individuals. Alcohol and Alcoholism. 2016, 51(5):549-54. PubMed ID: 27117237
   
   

   This study demonstrates that GABRA2 (rs279858) genotype has an indirect effect on drinking through subjective response. Furthermore, it also indicates that the influence of SR on developing dependence differs based on rs279858 genotype.

4. Trucco E.M., et al. Susceptibility effects of GABA receptor subunit alpha-2 (GABRA2) variants and parental monitoring on externalizing behavior trajectories: Risk and protection conveyed by the minor allele. Development and psychopathology. 2016, 28(1):15-26. PubMed ID: 25797587
   
   

   This report finds that there exist three externalizing trajectory classes (i.e., low, decreasing, and high) across adolescence. Furthermore, a GABRA2 × Parental Monitoring effect on class membership is observed, such that A-carriers are largely unaffected by parental monitoring, whereas class membership for those with the GG genotype is affected by parental monitoring.

5. Strac D.S., et al. Association of GABAA receptor α2 subunit gene (GABRA2) with alcohol dependence-related aggressive behavior. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2015, 63:119-25. PubMed ID: 26116794
   
   

   This article aims to examine the allelic and haplotypic association of the GABRA2 gene with alcohol dependence and related aggressive behavior in subjects of Eastern European (Croatian) origin. It indicates that the GABRA2 gene is associated with alcohol dependence-related aggressive behavior.

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