GABRE Membrane Protein Introduction

Introduction of GABRE

Gamma-aminobutyric acid receptor subunit epsilon (GABRE), also known as GABA(A) receptor subunit epsilon, is a protein that in humans is encoded by the GABRE gene. It belongs to the GABAA receptors family, which are the major inhibitory neurotransmitter in the adult CNS and mediated by the activation of ionotropic and metabotropic receptors.

Function of GABRE Membrane Protein

GABAA receptors are members of the evolutionarily related superfamily of ligand-gated ion channels in which heterologous subunits comprise a pentameric protein complex. Lonotropic GABAA receptors are heteropentameric structures generated by coassembly of α1-6, β1-3, γ1-3, ε, θ and π subunits. In GABA receptors, the subunit composition determines the affinity for GABA, the specific effects of allosteric modulators like benzodiazepines, which all stress the importance of increasing our knowledge of the molecular heterogeneity of native GABA receptors. As a member of the GABAA receptor, the epsilon subunit shares the greatest sequence homology with the γ subunits, and so it is generally thought to take the place of the γ subunit in the GABAA receptor. Studies have shown that the expression of ε subunit-containing GABAA receptors in the brainstem is upregulated during pregnancy, particularly in the ventral respiratory group.

Fig.1 GABAA receptor trafficking. (Tretter, 2008)

Application GABRE of Membrane Protein in Literature

1. Fang H., et al. Repeated inhalation of sevoflurane inhibits the information transmission of Purkinje cells and delays motor development via the GABAA receptor ε subunit in neonatal mice. Molecular medicine reports. 2018, 17 (1):1083-92. PubMed ID: 29115488
   
   

   This article suggests that GABAA-R ε subunit antagonists may be considered for combined application with general anesthesia with repeated inhalation of sevoflurane, for adverse effect prevention in the clinic.

2. Hengen K.B., et al. Increased GABAA receptor ε-subunit expression on ventral respiratory column neurons protects breathing during pregnancy. PLoS One. 2012, 7(1):e30608. PubMed ID: 22303446
   
   

   This article suggests that increased ε subunit expression may be critical to preserving respiratory function (and life) despite increased neurosteroid levels during pregnancy.

3. Hengen K.B., et al. Changes in ventral respiratory column GABAaR ε-and δ-subunits during hibernation mediate resistance to depression by EtOH and pentobarbital. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2010, 300(2):R272-83. PubMed ID: 21084677
   
   

   This article indicates that neuronal activity in the ventral respiratory column (VRC) during hibernation is unaffected by pentobarbital due to upregulation of ε-subunit-containing GABA(A)Rs on VRC neurons. Synaptic input from adjacent inhibitory interneurons that express δ-subunit-containing GABA(A)Rs is responsible for the excitatory effects of ethanol on VRC neurons during hibernation.

4. Belujon P., et al. Inhibitory transmission in locus coeruleus neurons expressing GABAA receptor epsilon subunit has a number of unique properties. Journal of neurophysiology. 2009, 102(4):2312-25. PubMed ID: 19625540
   
   

   This article aims to identify the synaptic transmission properties displayed by native receptors incorporating epsilon. It defines the signature of native GABA(A)R with a subunit composition including epsilon: differential sensitivity to FLU and DZP and slow rise time of currents.

5. Pape J.R., et al. Expression of GABAA receptor α3-, θ-, and ε-subunit mRNAs during rat CNS development and immunolocalization of the ε subunit in developing postnatal spinal cord. Neuroscience. 2009, 160(1):85-96. PubMed ID: 19249336
   
   

   This article suggests that various combinations of alpha3-, theta- and epsilon-subunits may be assembled at a regional and developmental level in the brain.

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Reference

1. Tretter, et al. (2008). GABAA receptor dynamics and constructing GABAergic synapses. Frontiers in molecular neuroscience. 1, 7.

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