GABRA4
Gamma-aminobutyric acid receptor subunit Alpha -4is aproteinthat in humans is encoded by theGABRA4gene.[5][6]
GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. At least 16 distinct subunits of GABA-A receptors have been identified.[6]
A research study compared wild-type to knockout GABRA4 gene in mice. It was determined that the elimination of the GABRA4 gene displayed characteristics that are associated with autism spectrum disorder (ASD). These include increased spatial cognition and decreased social engagement, unlike the wild-type mice. A hippocampal transcriptome analysis was profiled on knockout mice, showing the increased activity of N-methyl-D-aspartate receptors. This plays a role in consciousness and learning resulting in those characteristics.[7]
See also
[edit]References
[edit]- ^abcGRCh38: Ensembl release 89: ENSG00000109158–Ensembl,May 2017
- ^abcGRCm38: Ensembl release 89: ENSMUSG00000029211–Ensembl,May 2017
- ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^McLean PJ, Farb DH, Russek SJ (Aug 1995)."Mapping of the Alpha 4 subunit gene (GABRA4) to human chromosome 4 defines an Alpha 2- Alpha 4-beta 1-gamma 1 gene cluster: further evidence that modern GABAA receptor gene clusters are derived from an ancestral cluster".Genomics.26(3): 580–586.doi:10.1016/0888-7543(95)80178-O.PMID7607683.
- ^ab"Entrez Gene: GABRA4 gamma-aminobutyric acid (GABA) A receptor, Alpha 4".
- ^Fan C, Gao Y, Liang G, Huang L, Wang J, Yang X, Shi Y, Dräger UC, Zhong M, Gao TM, Yang X (December 2020)."Transcriptomics of Gabra4 knockout mice reveals common NMDAR pathways underlying autism, memory, and epilepsy | Molecular Autism".Molecular Autism.11(1): 13.doi:10.1186/s13229-020-0318-9.PMC7007694.PMID32033586.Retrieved2022-05-12.
Further reading
[edit]- Tögel M, Mossier B, Fuchs K, Sieghart W (1994)."gamma-Aminobutyric acidA receptors displaying association of gamma 3-subunits with beta 2/3 and different Alpha -subunits exhibit unique pharmacological properties".J. Biol. Chem.269(17): 12993–12998.doi:10.1016/S0021-9258(18)99974-6.PMID8175718.
- Yang W, Drewe JA, Lan NC (1996). "Cloning and characterization of the human GABAA receptor Alpha 4 subunit: identification of a unique diazepam-insensitive binding site".Eur. J. Pharmacol.291(3): 319–325.doi:10.1016/0922-4106(95)90072-1.PMID8719416.
- Kumar R, Lumsden A, Ciclitira PJ, et al. (2000). "Human genome search in celiac disease using gliadin cDNA as probe".J. Mol. Biol.300(5): 1155–1167.doi:10.1006/jmbi.2000.3927.PMID10903861.
- Kumar S, Sieghart W, Morrow AL (2002). "Association of protein kinase C with GABA(A) receptors containing Alpha 1 and Alpha 4 subunits in the cerebral cortex: selective effects of chronic ethanol consumption".J. Neurochem.82(1): 110–117.doi:10.1046/j.1471-4159.2002.00943.x.PMID12091471.S2CID82745932.
- Mu W, Cheng Q, Yang J, Burt DR (2002). "Alternative splicing of the GABA(A) receptor Alpha 4 subunit creates a severely truncated mRNA".Brain Res. Bull.58(5): 447–454.doi:10.1016/S0361-9230(02)00816-X.PMID12242096.S2CID140209801.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003)."Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences".Proc. Natl. Acad. Sci. U.S.A.99(26): 16899–16903.Bibcode:2002PNAS...9916899M.doi:10.1073/pnas.242603899.PMC139241.PMID12477932.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004)."Complete sequencing and characterization of 21,243 full-length human cDNAs".Nat. Genet.36(1): 40–45.doi:10.1038/ng1285.PMID14702039.
- Ma DQ, Whitehead PL, Menold MM, et al. (2006)."Identification of significant association and gene-gene interaction of GABA receptor subunit genes in autism".Am. J. Hum. Genet.77(3): 377–388.doi:10.1086/433195.PMC1226204.PMID16080114.
- Collins AL, Ma D, Whitehead PL, et al. (2007)."Investigation of autism and GABA receptor subunit genes in multiple ethnic groups".Neurogenetics.7(3): 167–174.doi:10.1007/s10048-006-0045-1.PMC1513515.PMID16770606.
- Lagrange AH, Botzolakis EJ, Macdonald RL (2007)."Enhanced macroscopic desensitization shapes the response of Alpha 4 subtype-containing GABAA receptors to synaptic and extrasynaptic GABA".J. Physiol.578(Pt 3): 655–676.doi:10.1113/jphysiol.2006.122135.PMC2151343.PMID17124266.
External links
[edit]- GABRA4+protein,+humanat the U.S. National Library of MedicineMedical Subject Headings(MeSH)
This article incorporates text from theUnited States National Library of Medicine,which is in thepublic domain.