GABRA1 Membrane Protein Introduction

Introduction of GABRA1

Gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1), also known as GABA(A) receptor subunit alpha-1, is a protein encoded by the human GABRA1 gene. It is a member of the type A γ-aminobutyric acid (GABAA) receptors which represent a large and diverse family of ligand-gated CI-channels that mediate the majority of fast inhibitory neurotransmission in the brain. As the specific target of the z-drug class of nonbenzodiazepine hypnotic agents, GABRA1 is responsible for their hypnotic and hallucinogenic effects.

Function of GABRA1 Membrane Protein

Gamma-aminobutyric acid (GABA)A receptors are characterized by extreme heterogeneity resulting from a large number of subunits forming this receptor. So far, as many as at least 20 subunits (α1−6, β1−3, γ1−3, δ, ε, θ, π, and ρ1−3) of this receptor have been cloned, which determine the receptor's agonist affinity, chance of opening, conductance, and other properties. As a member of the GABAA receptors family, the GABRA1 receptor is the specific target of the z-drug class of nonbenzodiazepine hypnotic agents and is responsible for their hypnotic and hallucinogenic effects. Studies have shown that GABAA receptors are widely distributed in all organisms that have a nervous system, which indicates that they play a role in virtually all brain functions. What’s more, it has been reported that GABRA1 is associated with hereditary generalized epilepsies, like juvenile myoclonic epilepsy, as well as sporadic epileptic encephalopathies, such as Dravet and Ohtahara syndromes.

Fig.1 Schematic structure of the GABAA receptor.

Application GABRA1 of Membrane Protein in Literature

1. Geng H.Y., et al. Erbb4 deletion from medium spiny neurons of the nucleus accumbens core induces schizophrenia-like behaviors via elevated GABAAR α1 expression. Journal of Neuroscience. 2017, 37(31):7450-7464. PubMed ID: 28667174
   
   

   This article suggests that the NAc core plays a role in the pathogenesis of schizophrenia and GABAAR α1 may be a potential pharmacological target for its treatment.

2. Bohnsack J.P., et al. Histone deacetylases mediate GABAA receptor expression, physiology, and behavioral maladaptations in rat models of alcohol dependence. Neuropsychopharmacology. 2018, 43(7):1518-1529. PubMed ID: 29520058
   
   

   This article shows how chronic ethanol exposure regulates the highly prominent GABAAR α1 subunit by an epigenetic mechanism, which represents a potential treatment modality for alcohol dependence.

3. Farnaes L., et al. Rapid whole-genome sequencing identifies a novel GABRA1 variant associated with West syndrome. Molecular Case Studies. 2017, 3(5). PubMed ID: 28864462
   
   

   This report suggests that GABRA1 mutations are associated with early infantile epileptic encephalopathy type 19 (EIEE19) and GABRA1 p.Met263Ile is associated with a distinct West syndrome phenotype.

4. Johannesen K., et al. Phenotypic spectrum of GABRA1: From generalized epilepsies to severe epileptic encephalopathies. Neurology. 2016, 87(11):1140-51. PubMed ID: 27521439
   
   

   This article aims to investigate the clinical features of a cohort of patients with GABRA1 gene mutations. It suggests that GABRA1 mutations make a significant contribution to the genetic etiology of both benign and severe epilepsy syndromes.

5. Baghel R, et.al. Evaluating the role of genetic variants on first-line antiepileptic drug response in North India: Significance of SCN1A and GABRA1 gene variants in phenytoin monotherapy and its serum drug levels. CNS neuroscience & therapeutics. 2016, 22(9):740-57. PubMed ID: 27245092
   
   

   This article aims to evaluate the association between genetic variants on drug response and therapy optimization parameters in patients treated with first-line antiepileptic drugs (AEDs). The results suggest that GABRA1 plays a role in phenytoin mode of action.

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