guest ::
| Home > Publications database > Mutations associated with epileptic encephalopathy modify EAAT2 anion channel function > print |
| Home > Publications database > Mutations associated with epileptic encephalopathy modify EAAT2 anion channel function > print |
| 001 | 904700 | ||
| 005 | 20230228125859.0 | ||
| 024 | 7 | _ | |a 10.1111/epi.17154 |2 doi |
| 024 | 7 | _ | |a 0013-9580 |2 ISSN |
| 024 | 7 | _ | |a 1528-1167 |2 ISSN |
| 024 | 7 | _ | |a altmetric:119938407 |2 altmetric |
| 024 | 7 | _ | |a pmid:34961934 |2 pmid |
| 024 | 7 | _ | |a WOS:000734862800001 |2 WOS |
| 024 | 7 | _ | |a 2128/31300 |2 Handle |
| 037 | _ | _ | |a FZJ-2022-00049 |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Kovermann, Peter |0 P:(DE-Juel1)156374 |b 0 |e Corresponding author |
| 245 | _ | _ | |a Mutations associated with epileptic encephalopathy modify EAAT2 anion channel function |
| 260 | _ | _ | |a Oxford [u.a.] |c 2022 |b Wiley-Blackwell |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1643883624_27540 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a Funding information: German Ministry of Education and Research, Grant Number: 01GM19007Early View: Onlinefirst |
| 520 | _ | _ | |a ObjectiveMutations in the gene solute carrier family member 1A2 (SLC1A2) encoding the excitatory amino acid transporter 2 (EAAT2) are associated with severe forms of epileptic encephalopathy. EAAT2 is expressed in glial cells and presynaptic nerve terminals and represents the main l-glutamate uptake carrier in the mammalian brain. It does not only function as a secondary active glutamate transporter, but also as an anion channel. How naturally occurring mutations affect these two transport functions of EAAT2 and how such alterations cause epilepsy is insufficiently understood.MethodsHere we studied the functional consequences of three disease-associated mutations, which predict amino acid exchanges p.Gly82Arg (G82R), p.Leu85Pro (L85P), and p.Pro289Arg (P289R), by heterologous expression in mammalian cells, biochemistry, confocal imaging, and whole-cell patch-clamp recordings of EAAT2 l-glutamate transport and anion current.ResultsG82R and L85P exchange amino acid residues contribute to the formation of the EAAT anion pore. They enlarge the pore diameter sufficiently to permit the passage of l-glutamate and thus function as l-glutamate efflux pathways. The mutation P289R decreases l-glutamate uptake, but increases anion currents despite a lower membrane expression.Significancel-glutamate permeability of the EAAT anion pore is an unexpected functional consequence of naturally occurring single amino acid substitutions. l-glutamate efflux through mutant EAAT2 anion channels will cause glutamate excitotoxicity and neuronal hyperexcitability in affected patients. Antagonists that selectively suppress the EAAT anion channel function could serve as therapeutic agents in the future. |
| 536 | _ | _ | |a 5244 - Information Processing in Neuronal Networks (POF4-524) |0 G:(DE-HGF)POF4-5244 |c POF4-524 |f POF IV |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, Journals: juser.fz-juelich.de |
| 700 | 1 | _ | |a Kolobkova, Yulia |0 P:(DE-Juel1)171438 |b 1 |
| 700 | 1 | _ | |a Franzen, Arne |0 P:(DE-Juel1)131923 |b 2 |u fzj |
| 700 | 1 | _ | |a Fahlke, Christoph |0 P:(DE-Juel1)136837 |b 3 |
| 773 | _ | _ | |a 10.1111/epi.17154 |g p. epi.17154 |0 PERI:(DE-600)2002194-X |n 2 |p 388-401 |t Epilepsia |v 63 |y 2022 |x 0013-9580 |
| 856 | 4 | _ | |u https://juser.fz-juelich.de/record/904700/files/Epilepsia%20-%202022%20-%20Kovermann%20-%20Mutations%20associated%20with%20epileptic%20encephalopathy%20modify%20EAAT2%20anion%20channel%20function.pdf |y OpenAccess |
| 909 | C | O | |o oai:juser.fz-juelich.de:904700 |p openaire |p open_access |p OpenAPC_DEAL |p driver |p VDB |p openCost |p dnbdelivery |
| 910 | 1 | _ | |a Forschungszentrum Jülich |0 I:(DE-588b)5008462-8 |k FZJ |b 0 |6 P:(DE-Juel1)156374 |
| 910 | 1 | _ | |a Forschungszentrum Jülich |0 I:(DE-588b)5008462-8 |k FZJ |b 2 |6 P:(DE-Juel1)131923 |
| 910 | 1 | _ | |a Forschungszentrum Jülich |0 I:(DE-588b)5008462-8 |k FZJ |b 3 |6 P:(DE-Juel1)136837 |
| 913 | 1 | _ | |a DE-HGF |b Key Technologies |l Natural, Artificial and Cognitive Information Processing |1 G:(DE-HGF)POF4-520 |0 G:(DE-HGF)POF4-524 |3 G:(DE-HGF)POF4 |2 G:(DE-HGF)POF4-500 |4 G:(DE-HGF)POF |v Molecular and Cellular Information Processing |9 G:(DE-HGF)POF4-5244 |x 0 |
| 914 | 1 | _ | |y 2022 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0160 |2 StatID |b Essential Science Indicators |d 2021-02-04 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1190 |2 StatID |b Biological Abstracts |d 2021-02-04 |
| 915 | _ | _ | |a Creative Commons Attribution-NonCommercial CC BY-NC 4.0 |0 LIC:(DE-HGF)CCBYNC4 |2 HGFVOC |
| 915 | _ | _ | |a DEAL Wiley |0 StatID:(DE-HGF)3001 |2 StatID |d 2021-02-04 |w ger |
| 915 | _ | _ | |a WoS |0 StatID:(DE-HGF)0113 |2 StatID |b Science Citation Index Expanded |d 2021-02-04 |
| 915 | _ | _ | |a OpenAccess |0 StatID:(DE-HGF)0510 |2 StatID |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0200 |2 StatID |b SCOPUS |d 2022-11-25 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0300 |2 StatID |b Medline |d 2022-11-25 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0199 |2 StatID |b Clarivate Analytics Master Journal List |d 2022-11-25 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0150 |2 StatID |b Web of Science Core Collection |d 2022-11-25 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1050 |2 StatID |b BIOSIS Previews |d 2022-11-25 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1110 |2 StatID |b Current Contents - Clinical Medicine |d 2022-11-25 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1030 |2 StatID |b Current Contents - Life Sciences |d 2022-11-25 |
| 915 | _ | _ | |a JCR |0 StatID:(DE-HGF)0100 |2 StatID |b EPILEPSIA : 2021 |d 2022-11-25 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0600 |2 StatID |b Ebsco Academic Search |d 2022-11-25 |
| 915 | _ | _ | |a Peer Review |0 StatID:(DE-HGF)0030 |2 StatID |b ASC |d 2022-11-25 |
| 915 | _ | _ | |a IF >= 5 |0 StatID:(DE-HGF)9905 |2 StatID |b EPILEPSIA : 2021 |d 2022-11-25 |
| 915 | p | c | |a APC keys set |2 APC |0 PC:(DE-HGF)0000 |
| 915 | p | c | |a Local Funding |2 APC |0 PC:(DE-HGF)0001 |
| 915 | p | c | |a DFG OA Publikationskosten |2 APC |0 PC:(DE-HGF)0002 |
| 915 | p | c | |a DEAL: Wiley 2019 |2 APC |0 PC:(DE-HGF)0120 |
| 920 | _ | _ | |l yes |
| 920 | 1 | _ | |0 I:(DE-Juel1)IBI-1-20200312 |k IBI-1 |l Molekular- und Zellphysiologie |x 0 |
| 980 | _ | _ | |a journal |
| 980 | _ | _ | |a VDB |
| 980 | _ | _ | |a UNRESTRICTED |
| 980 | _ | _ | |a I:(DE-Juel1)IBI-1-20200312 |
| 980 | _ | _ | |a APC |
| 980 | 1 | _ | |a APC |
| 980 | 1 | _ | |a FullTexts |
| Library | Collection | CLSMajor | CLSMinor | Language | Author |
|---|