GABRA5 Membrane Protein Introduction

Introduction of GABRA5

Gamma-aminobutyric acid (GABA)A receptor (GABRA5), also known as GABA-A receptor subunit alpha 5, is a protein which in humans is encoded by the GABRA5 gene. It belongs to the big gamma-aminobutyric acid (GABA) receptors family, which is a major inhibitory neurotransmitter in the mammalian central nervous system (CNS), that influences neuronal activity by activating ionotropic anion-conducting GABAA receptors (GABAARs) and metabotropic GABAB receptors.

Function of GABRA5 Membrane Protein

GABAARs are the members of the Cys-loop ligand-gated ion-channel family, which are composed of five subunits, assembled from a repertoire of 19 proteins. As a member of the GABAARs family, GABRA5 is mainly localized extrasynaptically and generate long-lasting tonic currents. Studies have shown that extrasynaptic GABRA5 is expressed in high levels in the hippocampus and at lower levels in the cortex, olfactory bulb, and hypothalamus. Activation of this receptor generates a tonic inhibitory conductance that reduces network excitability and synaptic plasticity. Furthermore, GABRA5 also plays a trophic role in learning and memory processes as well as regulating the development of neural circuits. Dysregulation of extrasynaptic GABAA receptors has been implicated in a variety of disorders including epilepsy, fragile X mental retardation, mood disorders and anesthetic-induced long-term memory disorders.

Fig.1 Structure of GABA receptors.

Application GABRA5 of Membrane Protein in Literature

1. Vidal V., et al. Decreasing the expression of GABAA α5 subunit-containing receptors partially improves cognitive, electrophysiological, and morphological hippocampal defects in the Ts65Dn model of Down Syndrome. Molecular Neurobiology. 2018, 55(6):4745-62. PubMed ID: 28717969
   
   

   This article suggests that reducing the expression of GABAA α5 receptors by deleting one or two copies of the Gabra5 gene in Ts65Dn (TS) mice partially ameliorates the cognitive impairments, improves long-term potentiation, enhances neural differentiation and maturation, and normalizes the density of the GABAergic synapse markers. It indicates that GABAAα5 plays a role in cognitive impairment in the TS mouse model of Down syndrome.

2. Perez-Sanchez J., et al. α5GABAA receptors mediate tonic inhibition in the spinal cord dorsal horn and contribute to the resolution of hyperalgesia. Journal of Neuroscience Research. 2017, 95(6):1307-18. PubMed ID: 27792253
   
   

   This article indicates that tonically-active α5GABAARs in the spinal cord dorsal horn could accelerate the resolution of hyperalgesia and may, therefore, serve as a novel therapeutic target to promote recovery from pathological pain.

3. Mesbah-Oskui L., et al. Reduced expression of α5GABAA receptors elicits autism-like alterations in EEG patterns and sleep-wake behavior. Neurotoxicology and Teratology. 2017, 61:115-22. PubMed ID: 27793660
   
   

   This article aims to evaluate the electroencephalogram (EEG) activity and sleep-wake behaviors in Gabra5-/- mice and wild-type mice. It suggests that reduced α5GABAAR activity contributes to an ASD phenotype and Gabra5-/- mice may serve as an animal model for ASD, as assessed through EEG activity and sleep-wake behaviors.

4. Piantadosi S.C., et al. Sex-dependent anti-stress effect of an α5 subunit containing GABAA receptor positive allosteric modulator. Frontiers in Pharmacology. 2016, 7:446. PubMed ID: 27920723
   
   

   This article aims to evaluate whether SH-053-2'F-R-CH3 (denoted "α5-PAM"), a positive allosteric modulator selective for α5-subunit containing GABAA receptors found predominantly on cortical pyramidal cell dendrites, has anti-stress effects. It suggests that acute and chronic positive modulation of α5 subunit-containing GABAA receptors elicits anti-stress effects in a sex-dependent manner, suggesting novel therapeutic modalities.

5. Cork S.C., et al. Altered GABAAα5 subunit expression in the hypothalamic paraventricular nucleus of hypertensive and pregnant rats. Neuroscience Letters. 2016, 620:148-53. PubMed ID: 27038517
   
   

   This study is conducted to investigate whether changes in subunit expression for GABAA receptors in the PVN could provide a molecular basis for the sympatho-excitation characteristic of hypertension and pregnancy. It suggests that decreases in the α5 subunit of the GABAA receptor may be important in mediating the sympatho-excitation observed in both hypertension and pregnancy.

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