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Human and Drosophila GABA B R2 have a related exon organization. (A) Exons containing coding sequence are indicated by fi lled boxes drawn to scale.
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The type B gamma-aminobutryic acid receptor (GABA(B)R) is a G protein coupled receptor that mediates slow pre- and post-synaptic inhibition in the nervous system. We find that the human GABA(B)R2 gene spans greater than 350 kb and contains 2.8 kb of coding region in 19 exons. The overall similarity in genomic structure with regard to conservation o...
Contexts in source publication
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... B Rs , GABA B R3 . The Drosophila genome has fi ve chromosomes and the chromosome arms are referred to as L and R (http:// fl ybase.bio.indiana.edu). The Drosophila GABA B R genes are located on two different chromosomes: 3R ( GABA R2 ) and 2L ( GABA R1 and GABA R3 ). Drosophila GABA B R1 and human GABA B R1b share 12 intron locations. The Drosophila GABA B R1 gene contains 13 exons. Drosophila GABA B Rs do not contain sushi domains that are found in the human GABA B R1a transcript (see Fig. 10B), although sushi domain sequences exist in the The size of introns in human GABA B R1 range from 97 to 7616 bp, in human GABA B R2 they range from 2697 to 112,150 bp, and in Drosophila GABA B R2 they range from 55 to 393 bp (Table 5). Intron size has therefore not been conserved between human and Drosophila GABA Rs . Drosophila genome. Drosophila GABA B R1 and human GABA B R1b have two exons, exons 2 and 3, with an identical number of bases, of 135 and 171 bp. Drosophila GABA B R1 exons, exons 4, 7, 9, 10 and 11, each correspond to two human GABA B R1 exons. The organization of the Drosophila GABA B R2 gene was determined by comparing Drosophila cDNA and genomic sequences (Table 4, Figs. 4 and 5). An alignment of Drosophila and human GABA B R2 genes reveals eight comparable intron locations (Fig. 5). Seven Drosophila GABA B R2 exons, exons 3 – 9, have the greatest similarity to human GABA B R2 and are between 49 – 56% identical at the nucleotide level. A single Drosophila GABA B R2 exon, exon 3, corresponds to four exons in human GABA B R2 , exons 2 – 5. Similarly, Drosophila GABA B R2 exons 6 and 7 each correspond to three human GABA B R2 exons, exons 8 – 10 and 11 – 13. Three Drosophila exons, exons 3, 6 and 7, and the comparable three regions in human GABA B R2 have a similar or identical number of bases (Fig. 5). In addition, two individual Drosophila GABA B R2 exons, exons 8 and 9, contain an identical number of bases as two human exons. Most differences between the human and Drosophila 0 0 0 GABA B R2 genes are located at the 5 and 3 ends. The 5 0 end of Drosophila GABA B R2 contains an intron in the 5 UTR that was not found in the human GABA B R2 gene, based upon the longest cDNA sequence available for human 0 GABA B R2 . The 3 end of Drosophila GABA B R2 is larger 0 than the 3 end of human GABA B R2 but both genes have 0 three introns in the 3 end that encodes the C-terminus. Each of the Drosophila GABA B R2 introns match the U2-Type GT-AG intron consensus (Table 3) and 5/12 introns inter- rupt a codon. The location of introns shared by human and Drosophila GABA B R2 argues that these orthologous genes arose from a common ancestral GABA R2 gene. Three GABA B R2 isoforms differing in their C-termini have been proposed to be a result of alternative mRNA splicing of two exons in the sequence encoding the GABA B R2 C- terminus (Clark et al., 2000). We fi nd that an alignment of the reported sequence of the cDNAs with GABA B R2 genomic sequence indicates that the sequences of the proposed alternative splicing lies within one exon, exon 19 of GABA B R2 (Fig. 6). To determine whether the absence of the expected genomic structure is due to a deletion, rearrangement, or error in the genomic sequence, different GABA B R2 genomic and cDNA sequences were compared (Fig. 6). The GABA B R2 exon 19 sequence derived from four genomic clones is identical in 44 overlapping human GABA B R2 ESTs (GenBank), ten human GABA B R2 cDNAs (GenBank), and 64 human adult and fetal brain GABA B R2 cDNAs (Martin et al., 1999), except for changes in certain single nucleotides. These results indicate that the genomic clone sequence ascribed to exon 19 (Figs. 1 and 6) is a true copy of the GABA B R2 genomic DNA and that the location of the proposed GABA B R2 alternative splicing is within exon 19. These results suggest that an alternative mechanism, such as intron retention, is required to explain the generation of the proposed GABA B R2 isoforms. Intron retention (Kilpatrick et al., 1999) is a mode of pre-mRNA splicing where an intron can be spliced or retained in the mature RNA as a result of the utilization of genomic sequence as an exon with respect to one transcript and as an intron with respect to another. (GABA B R2b) and ACAGA (GABA B R2c), fl ank the deleted sequence. In consequence, there are fi ve positions for GABA B R2b and six positions for GABA B R2c to examine and determine whether splice junctions exist at these loca- 0 0 tions (Table 6). However, no 5 splice donor or 3 splice acceptor sequences (Table 2) are found in exon 19 for any of the possible intron locations consistent with the formation of GABA B R2b or GABA B R2c . The GABA B R2 genomic sequence does not contain canonical splice sites for GABA R2b or GABA R2c . To determine whether the proposed GABA B R2b and GABA B R2c transcripts could have been generated by alternative splicing we asked whether exon 19 contains appro- priately located canonical splice sites. To look for the presence of splice sites in exon 19, the cDNA sequences of GABA B R2b and GABA B R2c were aligned with the exon 19 genomic sequence (Fig. 7). 0 Surprisingly, this alignment reveals a repeated sequence 5 0 and 3 of both deletions. The repeated sequences, CCAC GABA B R1a has fi ve additional 5 exons when compared 0 to GABA B R2 . Two of the fi ve 5 GABA B R1a exons encode two sushi domains (Fig. 8). Sushi domains are not found in GABA R1b or GABA R2. Each sushi domain has ...
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... B Rs , GABA B R3 . The Drosophila genome has fi ve chromosomes and the chromosome arms are referred to as L and R (http:// fl ybase.bio.indiana.edu). The Drosophila GABA B R genes are located on two different chromosomes: 3R ( GABA R2 ) and 2L ( GABA R1 and GABA R3 ). Drosophila GABA B R1 and human GABA B R1b share 12 intron locations. The Drosophila GABA B R1 gene contains 13 exons. Drosophila GABA B Rs do not contain sushi domains that are found in the human GABA B R1a transcript (see Fig. 10B), although sushi domain sequences exist in the The size of introns in human GABA B R1 range from 97 to 7616 bp, in human GABA B R2 they range from 2697 to 112,150 bp, and in Drosophila GABA B R2 they range from 55 to 393 bp (Table 5). Intron size has therefore not been conserved between human and Drosophila GABA Rs . Drosophila genome. Drosophila GABA B R1 and human GABA B R1b have two exons, exons 2 and 3, with an identical number of bases, of 135 and 171 bp. Drosophila GABA B R1 exons, exons 4, 7, 9, 10 and 11, each correspond to two human GABA B R1 exons. The organization of the Drosophila GABA B R2 gene was determined by comparing Drosophila cDNA and genomic sequences (Table 4, Figs. 4 and 5). An alignment of Drosophila and human GABA B R2 genes reveals eight comparable intron locations (Fig. 5). Seven Drosophila GABA B R2 exons, exons 3 – 9, have the greatest similarity to human GABA B R2 and are between 49 – 56% identical at the nucleotide level. A single Drosophila GABA B R2 exon, exon 3, corresponds to four exons in human GABA B R2 , exons 2 – 5. Similarly, Drosophila GABA B R2 exons 6 and 7 each correspond to three human GABA B R2 exons, exons 8 – 10 and 11 – 13. Three Drosophila exons, exons 3, 6 and 7, and the comparable three regions in human GABA B R2 have a similar or identical number of bases (Fig. 5). In addition, two individual Drosophila GABA B R2 exons, exons 8 and 9, contain an identical number of bases as two human exons. Most differences between the human and Drosophila 0 0 0 GABA B R2 genes are located at the 5 and 3 ends. The 5 0 end of Drosophila GABA B R2 contains an intron in the 5 UTR that was not found in the human GABA B R2 gene, based upon the longest cDNA sequence available for human 0 GABA B R2 . The 3 end of Drosophila GABA B R2 is larger 0 than the 3 end of human GABA B R2 but both genes have 0 three introns in the 3 end that encodes the C-terminus. Each of the Drosophila GABA B R2 introns match the U2-Type GT-AG intron consensus (Table 3) and 5/12 introns inter- rupt a codon. The location of introns shared by human and Drosophila GABA B R2 argues that these orthologous genes arose from a common ancestral GABA R2 gene. Three GABA B R2 isoforms differing in their C-termini have been proposed to be a result of alternative mRNA splicing of two exons in the sequence encoding the GABA B R2 C- terminus (Clark et al., 2000). We fi nd that an alignment of the reported sequence of the cDNAs with GABA B R2 genomic sequence indicates that the sequences of the proposed alternative splicing lies within one exon, exon 19 of GABA B R2 (Fig. 6). To determine whether the absence of the expected genomic structure is due to a deletion, rearrangement, or error in the genomic sequence, different GABA B R2 genomic and cDNA sequences were compared (Fig. 6). The GABA B R2 exon 19 sequence derived from four genomic clones is identical in 44 overlapping human GABA B R2 ESTs (GenBank), ten human GABA B R2 cDNAs (GenBank), and 64 human adult and fetal brain GABA B R2 cDNAs (Martin et al., 1999), except for changes in certain single nucleotides. These results indicate that the genomic clone sequence ascribed to exon 19 (Figs. 1 and 6) is a true copy of the GABA B R2 genomic DNA and that the location of the proposed GABA B R2 alternative splicing is within exon 19. These results suggest that an alternative mechanism, such as intron retention, is required to explain the generation of the proposed GABA B R2 isoforms. Intron retention (Kilpatrick et al., 1999) is a mode of pre-mRNA splicing where an intron can be spliced or retained in the mature RNA as a result of the utilization of genomic sequence as an exon with respect to one transcript and as an intron with respect to another. (GABA B R2b) and ACAGA (GABA B R2c), fl ank the deleted sequence. In consequence, there are fi ve positions for GABA B R2b and six positions for GABA B R2c to examine and determine whether splice junctions exist at these loca- 0 0 tions (Table 6). However, no 5 splice donor or 3 splice acceptor sequences (Table 2) are found in exon 19 for any of the possible intron locations consistent with the formation of GABA B R2b or GABA B R2c . The GABA B R2 genomic sequence does not contain canonical splice sites for GABA R2b or GABA R2c . To determine whether the proposed GABA B R2b and GABA B R2c transcripts could have been generated by alternative splicing we asked whether exon 19 contains appro- priately located canonical splice sites. To look for the presence of splice sites in exon 19, the cDNA sequences of GABA B R2b and GABA B R2c were aligned with the exon 19 genomic sequence (Fig. 7). 0 Surprisingly, this alignment reveals a repeated sequence 5 0 and 3 of both deletions. The repeated sequences, CCAC GABA B R1a has fi ve additional 5 exons when compared 0 to GABA B R2 . Two of the fi ve 5 GABA B R1a exons encode two sushi domains (Fig. 8). Sushi domains are not found in GABA R1b or GABA R2. Each sushi domain has ...
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... organization of the Drosophila GABA B R2 gene was determined by comparing Drosophila cDNA and genomic sequences ( Table 4, Figs. 4 and 5). An alignment of Droso- phila and human GABA B R2 genes reveals eight comparable intron locations (Fig. 5). Seven Drosophila GABA B R2 exons, exons 3-9, have the greatest similarity to human GABA B R2 and are between 49-56% identical at the nucleo- tide level. A single Drosophila GABA B R2 exon, exon 3, corresponds to four exons in ...
Context 4
... organization of the Drosophila GABA B R2 gene was determined by comparing Drosophila cDNA and genomic sequences ( Table 4, Figs. 4 and 5). An alignment of Droso- phila and human GABA B R2 genes reveals eight comparable intron locations (Fig. 5). Seven Drosophila GABA B R2 exons, exons 3-9, have the greatest similarity to human GABA B R2 and are between 49-56% identical at the nucleo- tide level. A single Drosophila GABA B R2 exon, exon 3, corresponds to four exons in human GABA B R2, exons 2-5. Similarly, Drosophila GABA B R2 exons 6 and 7 each corre- spond to three human ...
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... GABA B R2 exon, exon 3, corresponds to four exons in human GABA B R2, exons 2-5. Similarly, Drosophila GABA B R2 exons 6 and 7 each corre- spond to three human GABA B R2 exons, exons 8-10 and 11- 13. Three Drosophila exons, exons 3, 6 and 7, and the comparable three regions in human GABA B R2 have a simi- lar or identical number of bases (Fig. 5). In addition, two individual Drosophila GABA B R2 exons, exons 8 and 9, contain an identical number of bases as two human ...
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... RT-qPCR was performed as described in our previous study (He et al., 2011(He et al., , 2022 We used the primers amplifying sequence from exon 2 through exon 6 of GABBR1 (NM_001470.4) to identify GABBR1a (containing 2 sushi domains on exon 3 and 4) and GABBR1c (containing 1 sushi domain on exon 3), according to previous studies (Bettler et al., 2004;Lee et al., 2010;Martin et al., 2001). Primers for human GABBR1a (product size 563 bp) and GABBR1c (product size 377 bp) were forward 5′ CAGAT CAT ACA CCC GCCCTG3′ and reverse 5′CTGTC GTG GTG GAT GAGCTT3′. ...
Beta‐site amyloid precursor protein (APP)‐cleaving enzyme 2 (BACE2) is highly expressed in cerebrovascular endothelium. Notably, BACE2 is one of the most downregulated genes in cerebrovascular endothelium derived from patients with Alzheimer's disease. The present study was designed to determine the role of BACE2 in control of expression and function of endothelial nitric oxide synthase (eNOS). Genetic downregulation of BACE2 with small interfering RNA (BACE2siRNA) in human brain microvascular endothelial cells (BMECs) significantly decreased expression of eNOS and elevated levels of eNOS phosphorylated at threonine residue Thr495, thus leading to reduced production of nitric oxide (NO). BACE2siRNA also suppressed expression of APP and decreased production and release of soluble APPα (sAPPα). In contrast, adenovirus‐mediated overexpression of APP increased expression of eNOS. Consistent with these observations, nanomolar concentrations of sAPPα and APP 17mer peptide (derived from sAPPα) augmented eNOS expression. Further analysis established that γ‐aminobutyric acid type B receptor subunit 1 and Krüppel‐like factor 2 may function as downstream molecular targets significantly contributing to BACE2/APP/sAPPα‐induced up‐regulation of eNOS. In agreement with studies on cultured human endothelium, endothelium‐dependent relaxations to acetylcholine and basal production of cyclic GMP were impaired in cerebral arteries of BACE2‐deficient mice. We propose that in the brain blood vessels, BACE2 may function as a vascular protective protein. image
... Both isoforms are not splice variants, but have a different transcriptional start. The start of the GABAB1b isoform is located in the GABAB1a intron upstream of the exon VI and ends at 5´end of exon VI (Pfaff et al., 1999;Martin et al., 2001). The different transcriptional starts lead to a discrepancy in the N-terminus and in the sushi domains (also known as short consensus repeats), which play a role in protein interactions. ...
... Despite the marginal association in the validation study, given the rigor of our multistage study algorithm, including stringent control for false-discovery rate in the Replication stage, and the similar magnitude and direction of the survival effects, we accept this as strong evidence of the observed survival association. The validated locus is situated in the gene body of Gamma-Aminobutyric Acid B Receptor 1 (GABBR1), a gene encoding a receptor for a major inhibitory neurotransmitter for which multiple transcript variants have been identified [37]. We did not, however, observe a significant relationship with GABBR1 expression using the mRNA-sequencing data for 85 OSCC tumors available through TCGA (data not shown), although we cannot rule out a trans effect on the transcription of other genes. ...
Objectives
The objective of this study was to identify novel survival-associated biomarkers in oral rinse samples collected from patients with oral squamous cell carcinoma (OSCC).
Materials and methods
We screened for putative survival-associated markers using publicly available methylation array data from 88 OSCC tumors. Cox models were then fit to methylation array data restricted to these putative loci in oral rinse samples of 82 OSCC patients from greater Boston. Pyrosequencing assays were designed for each locus that replicated in the oral rinse samples and applied to a validation set of oral rinse samples from another 61 OSCC patients.
Results
We identified 7 survival-associated methylation markers in oral rinse samples from OSCC patients, and have validated one, located in the body of GABBR1, by pyrosequencing.
Conclusion
The 7 CpG loci identified through this study represent novel prognostic biomarkers for patients with OSCC that can be detected using a non-invasive oral rinse collection technique.
... GABA B1c transcripts were detected in human and rat (Fig. 2). The expression pattern of human GABA B1c mRNA parallels that of GABA B1a (Martin et al. 2001). It would be interesting to know whether a single SD is enough to guide GABA B1c to its appropriate destinations. ...
γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the vertebrate central nervous system. Metabotropic GABA(B) receptors are heterodimeric G-protein-coupled receptors (GPCRs) consisting of GABA(B1) and GABA(B2) subunits. The intracellular C-terminal domains of GABA(B) receptors are involved in heterodimerization, oligomerization, and association with other proteins, which results in a large receptor complex. Multiple splice variants of the GABA(B1) subunit have been identified in which GABA(B1a) and GABA(B1b) are the most abundant isoforms in the nervous system. Isoforms GABA(B1c) through GABA(B1n) are minor isoforms and are detectable only at mRNA levels. Some of the minor isoforms have been detected in peripheral tissues and encode putative soluble proteins with C-terminal truncations. Interestingly, increased expression of GABA(B) receptors has been detected in several human cancer cells and tissues. Moreover, GABA(B) receptor agonist baclofen inhibited tumor growth in rat models. GABA(B) receptor activation not only induces suppressing the proliferation and migration of various human tumor cells but also results in inactivation of CREB (cAMP-responsive element binding protein) and ERK in tumor cells. Their structural complexity makes it possible to disrupt the functions of GABA(B) receptors in various ways, raising GABA(B) receptor diversity as a potential therapeutic target in some human cancers.
... In addition, the GABA B1j subunit (190aa), a small C-terminal truncated GABA B1 isoform which was found to be expressed as highly as GABA B1a and GABA B1b subunits in brain, is a soluble isoform with the sushi domains which selectively impair the function of presynaptic (but not postsynaptic) GABA B receptors [32]. Interestingly, the two described isoforms of the GABA B2 subunit do not match consensus sequences for splice junctions, suggesting that they likely represent artifacts during cloning process [33]. Overall, the GABA B1 subunit alternative splicing provides a large diversity of structural and functional variation in GABA B1 receptors, and thus the existence of two main isoforms, GABA B1a and GABA B1b , which are highly conserved among different species, is the best evidence for molecular and functional heterogeneity of GABA B receptors. ...
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... This implicates the modified GABAbR1 gene on chromosome 6p21.3 (Martin et al. 2001) as a major contributor to schizophrenia. Since the inheritance of schizophrenia is multigenic (Freedman et al. 2001), the gene identified by Freedman, Leonard and collaborators is also strongly implicated, a gene that causes altered expression of the alpha-7 nicotinic receptor. ...
... It is reasonable to assume that presynaptic inhibition in the caudate nucleus depends on the GABAbR1 receptor subunit coded by the gene on chromosome 6p21.3 (Martin et al. 2001). This could explain the genetic advantage. ...
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... The GABA B receptor is a G i /G o protein-coupled receptor heterodimer with two subunits, designated 1 and 2. Activation at this site produces neuronal hyperpolarization by increasing membrane K + conductance. The antispastic agent (-)-baclofen is a highly selective agonist for GABA B receptors ( Martin et al., 2001). Saclofen, a GABA B receptor antagonist, had to be injected into the septum at a higher dose in 12-than in 4-month-old mice to improve retention in SAMP8 mice after training on footshock avoidance ( Flood et al., 1998), suggesting a possible upregulation of GABA B receptor. ...
... Both gastric and intestinal regions displayed mucosal GABA B immunoreacticity , however gastric GABA B -positive cells tended to contain Partial cDNAs corresponding to putative GABA B2 splice variants have also been isolated (Clark et al., 2000). However, investigation of the Gpr51 (Gabbr2) gene structure did not provide evidence that these cDNAs correspond to additional GABA B2 splice variants (Martin et al., 2001). Furthermore, the absence of an expression profile for GABA B2a , GABA B2b , and GABA B2c in the human GI tract would suggest such splice variants do not play a significant role in GI function (Calver et al., 2000). ...
γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the body and hence GABA-mediated neurotransmission regulates many physiological functions, including those in the gastrointestinal (GI) tract. GABA is located throughout the GI tract and is found in enteric nerves as well as in endocrine-like cells, implicating GABA as both a neurotransmitter and an endocrine mediator influencing GI function. GABA mediates its effects via GABA receptors which are either ionotropic GABAA or metabotropic GABAB. The latter which respond to the agonist baclofen have been least characterized, however accumulating data suggest that they play a key role in GI function in health and disease. Like GABA, GABAB receptors have been detected throughout the gut of several species in the enteric nervous system, muscle, epithelial layers as well as on endocrine-like cells. Such widespread distribution of this metabotropic GABA receptor is consistent with its significant modulatory role over intestinal motility, gastric emptying, gastric acid secretion, transient lower esophageal sphincter relaxation and visceral sensation of painful colonic stimuli. More intriguing findings, the mechanisms underlying which have yet to be determined, suggest GABAB receptors inhibit GI carcinogenesis and tumor growth. Therefore, the diversity of GI functions regulated by GABAB receptors makes it a potentially useful target in the treatment of several GI disorders. In light of the development of novel compounds such as peripherally acting GABAB receptor agonists, positive allosteric modulators of the GABAB receptor and GABA producing enteric bacteria, we review and summarize current knowledge on the function of GABAB receptors within the GI tract.
... The structure of the extracellular region of the two GABA-binding GPCRs, GABABR1 (GABABR1a-c 155,156 ) and GABABR2 (Ref. 155), differ slightly from the GRMs CASR and TAS1Rs (fIG. ...
G protein-coupled receptors (GPCRs) are the largest family of membrane-bound receptors and also the targets of many drugs. Understanding of the functional significance of the wide structural diversity of GPCRs has been aided considerably in recent years by the sequencing of the human genome and by structural studies, and has important implications for the future therapeutic potential of targeting this receptor family. This article aims to provide a comprehensive overview of the five main human GPCR families--Rhodopsin, Secretin, Adhesion, Glutamate and Frizzled/Taste2--with a focus on gene repertoire, general ligand preference, common and unique structural features, and the potential for future drug discovery.
... In contrast, the metabotropic GABA B R is made up of two distinct subunits GABA B R1 and GABA B R2. It is now clear that the most abundant GABA B R1 isoforms (GABA B R1a and GABA B R1b) are produced by alternative promoters in the GABA B R1 gene (6), and there is no evidence for GABA B 2 variants (7). ...
... Contrary to this expectation, the human GABA B R1 gene has been mapped (Fig. 1). The majority of exon locations and sizes are conserved between orthologues and paraloques in human and Drosophila, suggesting an ancestral gene (7). The GABA B R1 coding region spans 22 kb, whereas the GABA B R2 coding region spans 418 kb of genomic DNA. ...
... The human GABA B R1c isoform is predicted to encode a protein with only the first of the two SD present in GABA B R1a (Fig. 9). Similar to patterns of GABA B R1a expression, GABA B R1c mRNA is more highly expressed in early nervous system development when compared with adult levels (7), suggesting that the two isoforms are coordinately regulated (Fig. 10). The functional significance of two SD in GABA B R1a or one sushi domain in GABA B R1c remains to be determined in future studies. ...
The γ-aminobutyric acid (GABA) neurotransmitter acting through ionotropic and metabotropic receptor classes exerts the major
inhibitory control in the central nervous system. Therapeutic agents targeting GABA receptors (GABA-R), such as benzodiazepines
and baclofen, are used to treat many nervous system conditions, including anxiety and spasticity. The subunit composition
of GABA-Rs at the cell surface plays a critical role in determining their physiological and pharmacological properties, and
alteration of GABA-R subunit expression has been associated with a number of diseases including schizophrenia, temporal lobe
epilepsy, and alcoholism. The ionotropic type A GABA receptor (GABAAR) and type C GABA receptor (GABACR) are pentameric complexes that comprise a ligand gated chloride channel. The metabotropic type B GABA receptor (GABABR) is a heterodimer that couples G protein-signaling to GABA binding. There are eight classes of ionotropic receptor subunits
and only two metabotropic receptor subunit classes. Most of the GABAAR subunit genes are localized in syntenic β-α-γ gene clusters on four chromosomes but the two GABABR genes are localized on distinct chromosomes. Control over subunit expression in different brain regions and during development
is orchestrated at the genomic level by the use of multiple promoter regions and through the alternative splicing of GABA-R
subunit RNAs. This chapter examines current GABA-R research relevant to the many levels of control over receptor gene regulation
and cell surface receptor expression that may be relevant to both health and disease.
