GABRD Membrane Protein Introduction

Introduction of GABRD

Gamma-aminobutyric acid receptor subunit delta (GABRD), also known as GABA(A) receptor subunit delta, is a protein that in humans is encoded by the GABRD gene. It is a member of the GABAA receptors (GABAARs), which are composed of different subunits arranged in pentameric assemblies, with specific subunit compositions determining their regional distribution, kinetics, and pharmacology.

Function of GABRD Membrane Protein

GABAA receptors containing δ subunits (δ-GABAARs) are GABA-gated ion channels with extra- and perisynaptic localization, strong sensitivity to neurosteroids (NS), and a high degree of plasticity. As a member of the GABAA receptors, GABRD is a high affinity, low efficacy non-synaptic GABAA receptor with a high sensitivity to neurosteroids. Recently, GABRD receptor has attracted considerable attention as it could significantly reduce neuronal excitability in vitro and also regulate neurogenesis, memory, nociception, maternal behaviors, and responses to stress. It also functions to dampen network excitability and prevent excessive excitation. What’s more, studies have shown that dysregulation of GABRD receptor expression may be involved with several disorders, including neurodegenerative diseases, stroke, depression, epilepsy, schizophrenia, and traumatic brain injury.

Fig.1 The Structure of GABAA Receptor Subunit. (Charych, 2009)

Application GABRD of Membrane Protein in Literature

1. Xu W., et al. Sperm gamma-aminobutyric acid type A receptor delta subunit (GABRD) and its interaction with purinergic P2X2 receptors in progesterone-induced acrosome reaction and male fertility. Reproduction, Fertility, and Development. 2017, 29(10):2060-72. PubMed ID: 28190421
   
   

   This article aims to study the expression of gamma-aminobutyric acid type A receptor delta subunit (GABRD) in human and rodent sperm and its involvement in mediating the progesterone-induced acrosome reaction. It suggests that GABRD represents a novel progesterone receptor or modulator in spermatozoa that is responsible for the progesterone-induced Ca²⁺ influx required for the acrosome reaction through its interaction with the P2X2 receptor.

2. Montandon G., et al. δ-Subunit containing GABAA receptors modulate respiratory networks. Scientific reports. 2017, 7(1):18105. PubMed ID: 29273726
   
   

   This article indicates that δGABAARs are involved in the modulating of the respiratory network, which is critical to understand how δGABAARs change breathing in pathological conditions affecting extra-synaptic GABAA receptor function such as exposure to anesthetics and neurosteroids.

3. Whissell P.D., et al. δGABAA receptors are necessary for synaptic plasticity in the hippocampus: implications for memory behavior. Anesthesia & Analgesia. 2016, 123(5):1247-52. PubMed ID: 27464975
   
   

   This article suggests that δGABAA receptors are necessary for synaptic plasticity in the CA3 subfield. Drugs that enhance δGABAA receptor function may reverse deficits in synaptic plasticity in the CA3 subfield and improve pattern separation in neurological disorders.

4. Cushman J.D., et al. The role of the δ GABA (A) receptor in ovarian cycle-linked changes in hippocampus-dependent learning and memory. Neurochemical research. 2014, 39(6):1140-6. PubMed ID: 24667980
   
   

   This article suggests that δ-GABAAR plays an important role in estrous cycle-mediated fluctuations in hippocampus-dependent learning and memory.

5. Lee V., et al. Loss of Gabrd in CRH neurons blunts the corticosterone response to stress and diminishes stress-related behaviors. Psychoneuroendocrinology. 2014, 41:75-88. PubMed ID: 24495609
   
   

   This article shows the importance of the GABAAR δ subunit in the regulation of CRH neurons, and thus the HPA axis, and demonstrate that dysregulation of CRH neurons alters stress-related behaviors.

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Reference

1. Charych, et al. (2009). GABAA receptors and their associated proteins: Implications in the etiology and treatment of schizophrenia and related disorders. Neuropharmacology. 57(5-6), 481-495.

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