GABRB1 Membrane Protein Introduction

Introduction of GABRB1

Gamma-aminobutyric acid receptor subunit beta-1 (GABRB1), also known as GABA(B) receptor subunit beta-1, is a protein that in humans is encoded by the GABRB1 gene. It is a member of the GABAB receptors which mediate the metabotropic signaling of the inhibitory neurotransmitter. During the past years, functions and applications of GABRB1 have been widely studied.

Basic Information of GABRB1
Protein Name	Gamma-aminobutyric acid receptor subunit beta-1
Gene Name	GABRB1
Aliases	GABA(B) receptor subunit beta-1
Organism	Homo sapiens (Human)
UniProt ID	P18505
Transmembrane Times	4
Length (aa)	474
Sequence	MWTVQNRESLGLLSFPVMITMVCCAHSTNEPSNMSYVKETVDRLLKGYDIRLRPDFGGPPVDVGMRIDVASIDMVSEVNMDYTLTMYFQQSWKDKRLSYSGIPLNLTLDNRVADQLWVPDTYFLNDKKSFVHGVTVKNRMIRLHPDGTVLYGLRITTTAACMMDLRRYPLDEQNCTLEIESYGYTTDDIEFYWNGGEGAVTGVNKIELPQFSIVDYKMVSKKVEFTTGAYPRLSLSFRLKRNIGYFILQTYMPSTLITILSWVSFWINYDASAARVALGITTVLTMTTISTHLRETLPKIPYVKAIDIYLMGCFVFVFLALLEYAFVNYIFFGKGPQKKGASKQDQSANEKNKLEMNKVQVDAHGNILLSTLEIRNETSGSEVLTSVSDPKATMYSYDSASIQYRKPLSSREAYGRALDRHGVPSKGRIRRRASQLKVKIPDLTDVNSIDKWSRMFFPITFSLFNVVYWLYYVH

Function of GABRB1 Membrane Protein

GABAB receptors are multimeric assemblies of the GABAB1 and GABAB2 receptor subunits and K⁺ channel tetramerization-domain (KCTD) auxiliary proteins. To date, two predominant isoforms of the GABAB1 subunit in neurons have been identified, namely GABAB1a and GABAB1b, both of which heterodimerize with the GABAB2 subunit. The GABAB1a subunit isoform differs from the GABAB1b isoform by the presence of two sushi domains at the N-terminus which convey trafficking to distinct synaptic sites. Specifically, receptors assemble with the GABAB1a and GABAB1b subunits predominantly localized to presynaptic and postsynaptic sites, respectively. A series of studies have shown that GABAB receptors are associated with the modulation of dopaminergic neurotransmission and reward.

Fig.1 Structural organization of GABAB receptors and effector systems. (Benke, 2015)

Application GABRB1 of Membrane Protein in Literature

Duka T., et al. GABRB1 single nucleotide polymorphism associated with altered brain responses (but not performance) during measures of impulsivity and reward sensitivity in human adolescents. Frontiers in behavioral neuroscience. 2017, 11:24. PubMed ID: 28261068

This article suggests that β1-containing GABAA receptors may play a role in excitability of brain regions important in controlling reward-related behavior, which may contribute to susceptibility to addictive behavior.
Jacobson L.H., et al. Differential roles of GABAB1 subunit isoforms on locomotor responses to acute and repeated administration of cocaine. Behavioral brain research. 2016, 298:12-6. PubMed ID: 26518330

This article aims to investigate the responses of GABAB1 subunit isoform null mice to cocaine in acute locomotor activity and conditioned place preference (CPP) paradigms. It indicates that GABAB1a and GABAB1b isoforms differentially regulate behavioral responses to cocaine, with deletion of GABAB1a enhancing cocaine-induced locomotor activity and deletion of GABAB1b protecting from cocaine-induced sensitization.
Zhu B., et al. The GABRB1 gene is associated with thalamus volume and modulates the association between thalamus volume and intelligence. Neuroimage. 2014, 102:756-63. PubMed ID: 25192656

This article aims to verify the associations between GABRB1 variants, thalamus volume, and intelligence. It suggests that the GABRB1 gene is involved the thalamus structure and their interactive effects on intelligence.
Cheng Z.Y., et al. GABAB1 and GABAB2 receptor subunits co-expressed in cultured human RPE cells regulate intracellular Ca²⁺ via Gi/o-protein and phospholipase C pathways. Neuroscience. 2014, 280:254-61. PubMed ID: 25241062

This article is conducted to investigate whether the GABAB receptor subunits, GABAB1 and GABAB2, are co-expressed in cultured human RPE cells, and then determine if the GABAB receptor similarly regulates the [Ca(2+)] I of RPE cells and if phospholipase C is involved. It suggests that GABAB1 and GABAB2 are co-expressed in cell cultures of human RPE. Furthermore, GABAB receptors in RPE could regulate the [Ca(2+)] I via a Gi/o-protein and phospholipase C pathway.

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Reference

Benke D, et al. (2015). Regulation of cell surface GABAB receptors: contribution to synaptic plasticity in neurological diseases. Adv Pharmacol. 73, 41-70.

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