A novel de novo variant of GABRA1 causes increased sensitivity for GABA in vitro.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
11 02 2020
Historique:
received: 12 08 2019
accepted: 28 01 2020
entrez: 13 2 2020
pubmed: 13 2 2020
medline: 11 11 2020
Statut: epublish

Résumé

The GABRA1 gene encodes one of the most conserved and highly expressed subunits of the GABA

Identifiants

pubmed: 32047208
doi: 10.1038/s41598-020-59323-6
pii: 10.1038/s41598-020-59323-6
pmc: PMC7012862
doi:

Substances chimiques

GABA Modulators 0
GABRA1 protein, human 0
Receptors, GABA-A 0
gamma-Aminobutyric Acid 56-12-2
Diazepam Q3JTX2Q7TU

Types de publication

Case Reports Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2379

Subventions

Organisme : Austrian Science Fund FWF
ID : W 1232
Pays : Austria

Références

Olsen, R. W. & Sieghart, W. International Union of Pharmacology. LXX. Subtypes of gamma-aminobutyric acid(A) receptors: classification on the basis of subunit composition, pharmacology, and function. Update. Pharmacol. Rev. 60, 243–260 (2008).
pubmed: 18790874 doi: 10.1124/pr.108.00505 pmcid: 18790874
Kilb, W. Development of the GABAergic system from birth to adolescence. Neuroscientist 18, 613–630 (2012).
pubmed: 21952258 doi: 10.1177/1073858411422114 pmcid: 21952258
Zeilhofer, H. U., Wildner, H. & Yevenes, G. E. Fast synaptic inhibition in spinal sensory processing and pain control. Physiol. Rev. 92, 193–235 (2012).
pubmed: 22298656 pmcid: 3590010 doi: 10.1152/physrev.00043.2010
Araujo, F. et al. Molecular and pharmacological characterization of native cortical gamma-aminobutyric acidA receptors containing both alpha1 and alpha3 subunits. J. Biol. Chem. 271, 27902–27911 (1996).
pubmed: 8910390 doi: 10.1074/jbc.271.44.27902 pmcid: 8910390
Benke, D. et al. Analysis of the presence and abundance of GABAA receptors containing two different types of alpha subunits in murine brain using point-mutated alpha subunits. J Biol Chem 279 (2004).
Jechlinger, M., Pelz, R., Tretter, V., Klausberger, T. & Sieghart, W. Subunit composition and quantitative importance of hetero-oligomeric receptors: GABAA receptors containing alpha6 subunits. J. Neurosci. 18, 2449–2457 (1998).
pubmed: 9502805 pmcid: 6793083 doi: 10.1523/JNEUROSCI.18-07-02449.1998
Laurie, D. J., Wisden, W. & Seeburg, P. H. The distribution of thirteen GABAA receptor subunit mRNAs in the rat brain. III. Embryonic and postnatal development. J. Neurosci. 12, 4151–4172 (1992).
pubmed: 1331359 pmcid: 6576006 doi: 10.1523/JNEUROSCI.12-11-04151.1992
Wang, D. D. & Kriegstein, A. R. Defining the role of GABA in cortical development. J. Physiol. 587, 1873–1879 (2009).
pubmed: 19153158 pmcid: 2689328 doi: 10.1113/jphysiol.2008.167635
Wu, C. & Sun, D. GABA receptors in brain development, function, and injury. Metab. Brain Dis. 30, 367–379 (2015).
pubmed: 24820774 doi: 10.1007/s11011-014-9560-1 pmcid: 24820774
Tyzio, R. et al. Maternal oxytocin triggers a transient inhibitory switch in GABA signaling in the fetal brain during delivery. Sci. 314, 1788–1792 (2006).
doi: 10.1126/science.1133212
Fritschy, J. M., Paysan, J., Enna, A. & Mohler, H. Switch in the expression of rat GABAA-receptor subtypes during postnatal development: an immunohistochemical study. J. Neurosci. 14, 5302–5324 (1994).
pubmed: 8083738 pmcid: 6577100 doi: 10.1523/JNEUROSCI.14-09-05302.1994
Lopez-Tellez, J. F. et al. Postnatal development of the alpha1 containing GABAA receptor subunit in rat hippocampus. Brain Res. Dev. Brain Res 148, 129–141 (2004).
pubmed: 14757527 doi: 10.1016/j.devbrainres.2003.11.010 pmcid: 14757527
McKernan, R. M., Cox, P., Gillard, N. P. & Whiting, P. Differential expression of GABAA receptor alpha-subunits in rat brain during development. FEBS Lett. 286, 44–46 (1991).
pubmed: 1650715 doi: 10.1016/0014-5793(91)80936-W pmcid: 1650715
Duncan, C. E. et al. Prefrontal GABA(A) receptor alpha-subunit expression in normal postnatal human development and schizophrenia. J. Psychiatr. Res. 44, 673–681 (2010).
pubmed: 20100621 doi: 10.1016/j.jpsychires.2009.12.007 pmcid: 20100621
Pinto, J. G. A., Hornby, K. R., Jones, D. G. & Murphy, K. M. Developmental changes in GABAergic mechanisms in human visual cortex across the lifespan. Front. Cell Neurosci. 4, 16–16 (2010).
pubmed: 20592950 pmcid: 2893712
Ernst, M., Steudle, F. & Bampali, K. In eLS (John Wiley & Sons, Ltd, 2001).
Puthenkalam, R. et al. Structural Studies of GABA-A receptor binding sites: Which experimental structure tells us what? Front Mol Neurosci 9 (2016).
Hernandez, C. C. & Macdonald, R. L. A structural look at GABAA receptor mutations linked to epilepsy syndromes. Brain Res. 1714, 234–247 (2019).
pubmed: 30851244 doi: 10.1016/j.brainres.2019.03.004
Cossette, P. et al. Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy. Nat. Genet. 31, 184–189 (2002).
pubmed: 11992121 doi: 10.1038/ng885
Hirose, S. Mutant GABA(A) receptor subunits in genetic (idiopathic) epilepsy. Prog. Brain Res. 213, 55–85 (2014).
pubmed: 25194483 doi: 10.1016/B978-0-444-63326-2.00003-X pmcid: 25194483
Maljevic, S. et al. A mutation in the GABA(A) receptor alpha(1)-subunit is associated with absence epilepsy. Ann. Neurol. 59, 983–987 (2006).
pubmed: 16718694 doi: 10.1002/ana.20874 pmcid: 16718694
Johannesen, K. et al. Phenotypic spectrum of GABRA1: From generalized epilepsies to severe epileptic encephalopathies. Neurol. 87, 1140–1151 (2016).
doi: 10.1212/WNL.0000000000003087
Gallagher, M. J., Ding, L., Maheshwari, A. & Macdonald, R. L. The GABAA receptor alpha1 subunit epilepsy mutation A322D inhibits transmembrane helix formation and causes proteasomal degradation. Proc. Natl Acad. Sci. USA 104, 12999–13004 (2007).
pubmed: 17670950 doi: 10.1073/pnas.0700163104 pmcid: 17670950
Karczewski, K. J. et al. Variation across 141,456 human exomes and genomes reveals the spectrum of loss-of-function intolerance across human protein-coding genes. bioRxiv, 531210 (2019).
Kircher, M., Witten, D. M., Jain, P., O’Roak, B. J. & Cooper, G. M. A general framework for estimating the relative pathogenicity of human genetic variants. Nat. Genet. 46, 310–315 (2014).
pubmed: 24487276 pmcid: 3992975 doi: 10.1038/ng.2892
Rentzsch, P., Witten, D., Cooper, G. M., Shendure, J. & Kircher, M. CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic Acids Res. 47, D886–d894 (2019).
pubmed: 30371827 doi: 10.1093/nar/gky1016 pmcid: 30371827
Schwarz, J. M., Cooper, D. N., Schuelke, M. & Seelow, D. MutationTaster2: mutation prediction for the deep-sequencing age. Nat. Methods 11, 361 (2014).
pubmed: 24681721 doi: 10.1038/nmeth.2890 pmcid: 24681721
Sieghart, W. Allosteric modulation of GABAA receptors via multiple drug-binding sites. Adv. Pharmacol. 72, 53–96 (2015).
pubmed: 25600367 doi: 10.1016/bs.apha.2014.10.002 pmcid: 25600367
Absalom, N. L. et al. Functional genomics of epilepsy-associated mutations in the GABAA receptor subunits reveal that one mutation impairs function and two are catastrophic. J. Biol. Chem. 294, 6157–6171 (2019).
pubmed: 30728247 doi: 10.1074/jbc.RA118.005697 pmcid: 30728247
Eaton, M. M. et al. Gamma-aminobutyric acid type A alpha4, beta2, and delta subunits assemble to produce more than one functionally distinct receptor type. Mol. Pharmacol. 86, 647–656 (2014).
pubmed: 25238745 pmcid: 4244592 doi: 10.1124/mol.114.094813
Ahring, P. K. et al. A pharmacological assessment of agonists and modulators at alpha4beta2gamma2 and alpha4beta2delta GABAA receptors: The challenge in comparing apples with oranges. Pharmacol. Res. 111, 563–576 (2016).
pubmed: 27178730 doi: 10.1016/j.phrs.2016.05.014 pmcid: 27178730
Feng, H. J., Jounaidi, Y., Haburcak, M., Yang, X. & Forman, S. A. Etomidate produces similar allosteric modulation in α1β3δ and α1β3γ2L GABA(A) receptors. Br. J. Pharmacol. 171, 789–798 (2014).
pubmed: 24199598 pmcid: 3969089 doi: 10.1111/bph.12507
Simeone, X. et al. Molecular tools for GABAA receptors: High affinity ligands for β1-containing subtypes. Sci. Rep. 7, 5674 (2017).
pubmed: 28720884 pmcid: 5516028 doi: 10.1038/s41598-017-05757-4
Varagic, Z. et al. Identification of novel positive allosteric modulators and null modulators at the GABAA receptor alpha+beta- interface. Br. J. Pharmacol. 169, 371–383 (2013).
pubmed: 23472852 pmcid: 3651663 doi: 10.1111/bph.12151
Germann, A. L. et al. Steady-state activation and modulation of the synaptic-type alpha1beta2gamma2L GABAA receptor by combinations of physiological and clinical ligands. Physiol. Rep. 7, e14230 (2019).
pubmed: 31549483 pmcid: 6757177 doi: 10.14814/phy2.14230
Baburin, I. et al. Estimating the efficiency of benzodiazepines on GABA(A) receptors comprising gamma1 or gamma2 subunits. Br. J. Pharmacol. 155, 424–433 (2008).
pubmed: 18604239 pmcid: 2451336 doi: 10.1038/bjp.2008.271
Mortensen, M. & Smart, T. G. Extrasynaptic alphabeta subunit GABAA receptors on rat hippocampal pyramidal neurons. J. Physiol. 577, 841–856 (2006).
pubmed: 17023503 pmcid: 1890388 doi: 10.1113/jphysiol.2006.117952
Scott, S. & Aricescu, A. R. A structural perspective on GABAA receptor pharmacology. Curr. Opin. Struct. Biol. 54, 189–197 (2019).
pubmed: 31129381 doi: 10.1016/j.sbi.2019.03.023
Gravielle, M. C. Regulation of GABAA receptors by prolonged exposure to endogenous and exogenous ligands. Neurochem. Int. 118, 96–104 (2018).
pubmed: 29859230 doi: 10.1016/j.neuint.2018.05.015
Li, H. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. ArXiv 1303 (2013).
Van der Auwera, G. A. et al. From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline. Curr Protoc Bioinformatics 43, 11.10.11-33 (2013).
Wang, K., Li, M. & Hakonarson, H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38, e164 (2010).
pubmed: 20601685 pmcid: 20601685 doi: 10.1093/nar/gkq603
Stamenic, T. T. et al. Ester to amide substitution improves selectivity, efficacy and kinetic behavior of a benzodiazepine positive modulator of GABAA receptors containing the alpha5 subunit. Eur. J. Pharmacol. 791, 433–443 (2016).
pubmed: 27639297 pmcid: 5107132 doi: 10.1016/j.ejphar.2016.09.016
David, R. et al. Biochemical and functional properties of distinct nicotinic acetylcholine receptors in the superior cervical ganglion of mice with targeted deletions of nAChR subunit genes. Eur. J. Neurosci. 31, 978–993 (2010).
pubmed: 20377613 pmcid: 2989642 doi: 10.1111/j.1460-9568.2010.07133.x
Mossier, B., Togel, M., Fuchs, K. & Sieghart, W. Immunoaffinity purification of gamma-aminobutyric acidA (GABAA) receptors containing gamma 1-subunits. Evidence for the presence of a single type of gamma-subunit in GABAA receptors. J. Biol. Chem. 269, 25777–25782 (1994).
pubmed: 7929282 pmcid: 7929282
Gielen, M., Thomas, P. & Smart, T. G. The desensitization gate of inhibitory Cys-loop receptors. Nat. Commun. 6, 6829 (2015).
pubmed: 25891813 pmcid: 4410641 doi: 10.1038/ncomms7829
Masiulis, S. et al. GABAA receptor signalling mechanisms revealed by structural pharmacology. Nat. 565, 454–459 (2019).
doi: 10.1038/s41586-018-0832-5

Auteurs

Friederike Steudle (F)

Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University Vienna, Vienna, Austria.

Sabah Rehman (S)

Department of Molecular Neurosciences, Center for Brain Research, Medical University Vienna, Vienna, Austria.

Konstantina Bampali (K)

Department of Molecular Neurosciences, Center for Brain Research, Medical University Vienna, Vienna, Austria. konstantina.bampali@meduniwien.ac.at.

Xenia Simeone (X)

Department of Molecular Neurosciences, Center for Brain Research, Medical University Vienna, Vienna, Austria.

Zsofia Rona (Z)

Landesklinikum Thermenregion Mödling, Department of Pediatrics, Mödling, Austria.

Erwin Hauser (E)

Landesklinikum Thermenregion Mödling, Department of Pediatrics, Mödling, Austria.

Wolfgang M Schmidt (WM)

Neuromuscular Research Department, Center for Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria.

Petra Scholze (P)

Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University Vienna, Vienna, Austria.

Margot Ernst (M)

Department of Molecular Neurosciences, Center for Brain Research, Medical University Vienna, Vienna, Austria.

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