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GABRA4 Membrane Protein Introduction

Introduction of GABRA4

Gamma-aminobutyric acid receptor subunit alpha-4 (GABRA4), also known as GABA(A) receptor subunit alpha-4, is a protein that in humans is encoded by the GABRA4 gene. It is a member of the GABA(A) receptor family which are pentameric ligand-gated chloride channels (usually 2α, 2β, and δ or γ) that may be assembled from a large number of different subunit isoforms.

Basic Information of GABRA4
Protein Name Gamma-aminobutyric acid receptor subunit alpha-4
Gene Name GABRA4
Aliases GABA(A) receptor subunit alpha-4
Organism Homo sapiens (Human)
UniProt ID P48169
Transmembrane Times 4
Length (aa) 554
Sequence MVSAKKVPAIALSAGVSFALLRFLCLAVCLNESPGQNQKEEKLCTENFTRILDSLLDGYDNRLRPGFGGPVTEVKTDIYVTSFGPVSDVEMEYTMDVFFRQTWIDKRLKYDGPIEILRLNNMMVTKVWTPDTFFRNGKKSVSHNMTAPNKLFRIMRNGTILYTMRLTISAECPMRLVDFPMDGHACPLKFGSYAYPKSEMIYTWTKGPEKSVEVPKESSSLVQYDLIGQTVSSETIKSITGEYIVMTVYFHLRRKMGYFMIQTYIPCIMTVILSQVSFWINKESVPARTVFGITTVLTMTTLSISARHSLPKVSYATAMDWFIAVCFAFVFSALIEFAAVNYFTNIQMEKAKRKTSKPPQEVPAAPVQREKHPEAPLQNTNANLNMRKRTNALVHSESDVGNRTEVGNHSSKSSTVVQESSKGTPRSYLASSPNPFSRANAAETISAARALPSASPTSIRTGYMPRKASVGSASTRHVFGSRLQRIKTTVNTIGATGKLSATPPPSAPPPSGSGTSKIDKYARILFPVTFGAFNMVYWVVYLSKDTMEKSESLM

Function of GABRA4 Membrane Protein

The GABA(A) receptor is formed by the combination of multiple subunits determining agonist affinity, chance of opening and conductance of the receptor. Some factors such as different cell types, distinct brain regions, and hormonal fluctuations, as well as environmental changes or disease, both affect the expression of these subunits. Studies have shown that these subunits are encoded by different genes that display regional- and developmental-specific expression. As a member of the GABA(A) receptor family, GABRA4 is related to the control of cell proliferation, initial migration, and early dendritic development, indicating a key role in the regulation of adult neurogenesis. What’s more, it has been reported that the dramatic nature of Gabra4 plasticity makes it an interesting candidate to be involved in the long-lasting pathological conditions of CNS hyperexcitability that are often seen in individuals that experience several episodes of alcohol withdrawal (AW).

GABAA receptor structure. Fig.1 GABAA receptor structure. (Jacob, 2008)

Application GABRA4 of Membrane Protein in Literature

  1. Bekdash R.A and Harrison N.L. Downregulation of Gabra4 expression during alcohol withdrawal is mediated by specific microRNAs in cultured mouse cortical neurons. Brain and Behavior. 2015, 5(8):e00355. PubMed ID: 26357588

    This study aims to investigate the effects of alcohol use and withdrawal (AW) on changes in the expression of Gabra4 and related genes that encode other subunits of GABAARs, and the potential regulation of Gabra4 by microRNAs. It suggests that AW could decrease Gabra4 expression, and it may be mediated in part by the induction of specific microRNAs in cortical neurons during AW.

  2. Mo J., et al. Early growth response 1 (Egr-1) directly regulates GABAA receptor α2, α4, and θ subunits in the hippocampus. Journal of Neurochemistry. 2015, 133(4):489-500. PubMed ID: 25708312

    This article suggests that three GABAA receptor subunits, GABRA2 (α2), GABRA4 (α4), and GABRQ (θ) genes are transcriptional targets of Egr-1. Neuronal activity-dependent up-regulation of Egr-1 might lead to altered subtypes of GABAA receptors for the maintenance of homeostatic excitatory and inhibitory balance for the regulation of synaptic strength.

  3. Arbo B.D., et al. Asymmetric effects of low doses of progesterone on GABA(A) receptor α4 subunit protein expression in the olfactory bulb of female rats. Canadian Journal of Physiology and Pharmacology. 2014, 92(12):1045-9. PubMed ID: 25380418

    This study aims to evaluate the effect of progesterone on the protein expression of α4 subunit of GABA(A) receptor, serotonin transporter (SERT), Akt, Erk, and caspase-3 in the olfactory bulb (OB) of female rats exposed to the forced swimming test (FST). It suggests that progesterone has an asymmetric modulatory effect on the expression of GABA(A) receptor α4 subunit in the OB which may be related to the antidepressant-like effect of progesterone in female rats.

  4. Grabenstatter H.L., et al. Effect of spontaneous seizures on GABAA receptor α4 subunit expression in an animal model of temporal lobe epilepsy. Epilepsia. 2014, 55(11):1826-33. PubMed ID: 25223733

    This article suggests that spontaneous, recurrent seizures that define chronic epilepsy may influence changes in GABAA Rα4 expression, and that signaling pathways known to regulate GABAA Rα4 expression after status epilepticus may also be activated after spontaneous seizures in chronically epileptic animals.

GABRA4 Preparation Options

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Reference

  1. Jacob, et al. (2008). GABAA receptor trafficking and its role in the dynamic modulation of neuronal inhibition. Nature Reviews Neuroscience. 9(5), 331.

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