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  Dominance of the lurcher mutation in heteromeric kainate and AMPA receptor channels

Schwarz, M. K., Pawlak, V., Osten, P., Mack, V., Seeburg, P. H., & Köhr, G. (2001). Dominance of the lurcher mutation in heteromeric kainate and AMPA receptor channels. European Journal of Neuroscience: European Neuroscience Association, 14(5), 861-868. doi:10.1046/j.0953-816x.2001.01705.x.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-2223-0 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-2224-E
Genre: Journal Article
Alternative Title : Dominance of the lurcher mutation in heteromeric kainate and AMPA receptor channels

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EurJNeurosci_14_2001_861.pdf (Any fulltext), 241KB
 
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 Creators:
Schwarz, Martin K.1, Author              
Pawlak, Verena1, 2, Author              
Osten, Pavel1, Author              
Mack, Volker1, Author              
Seeburg, Peter H.1, Author              
Köhr, Georg1, 3, Author              
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              
2Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497701              
3Directly responsible to the Managing Director, Max Planck Institute for Medical Research, Max Planck Society, ou_persistent22              

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Free keywords: constitutive activation, HEK293 cells, pore size, surface expression, unliganded gating
 Abstract: Homomeric glutamate receptor (GluR) channels become spontaneously active when the last alanine residue within the invariant SYTANLAAF-motif in the third membrane segment is substituted by threonine. The same mutation in the orphan GluRdelta2 channel is responsible for neurodegeneration in "Lurcher" (Lc) mice. Since most native GluRs are composed of different subunits, we investigated the effect of an Lc-mutated subunit in heteromeric kainate and AMPA receptors expressed in HEK293 cells. Kainate receptor KA2 subunits, either wild type or carrying the Lc mutation (KA2(Lc)), are retained inside the cell but are surface-expressed when assembled with GluR6 subunits. Importantly, KA2(Lc) dominates the gating of KA2(Lc)/GluR6(WT) channels, as revealed by spontaneous activation and by slowed desensitization and deactivation kinetics of ligand-activated whole-cell currents. Moreover, the AMPA receptor subunit GluR-B(Lc)(Q) which forms spontaneously active homomeric channels with rectifying current-voltage relationships, dominates the gating of heteromeric GluR-B(Lc)(Q)/GluR-A(R) channels. The spontaneous currents of these heteromeric AMPAR channels show linear current-voltage relationships, and the ligand-activated whole-cell currents display slower deactivation and desensitization kinetics than the respective wild-type channels. For heteromeric Lc-mutated kainate and AMPA receptors, the effects on kinetics were reduced relative to the homomeric Lc-mutated forms. Thus, an Lc-mutated subunit can potentially influence heteromeric channel function in vivo, and the severity of the phenotype will critically depend on the levels of homomeric GluR(Lc) and heteromeric GluR(Lc)/GluR(WT) channels.

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Language(s): eng - English
 Dates: 2001-06-252001-02-212001-07-062001-12-202001-09-01
 Publication Status: Published in print
 Pages: 8
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: European Journal of Neuroscience : European Neuroscience Association
  Other : Eur. J. Neurosci
Source Genre: Journal
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Publ. Info: Oxford, UK : Published on behalf of the European Neuroscience Association by Oxford University Press
Pages: - Volume / Issue: 14 (5) Sequence Number: - Start / End Page: 861 - 868 Identifier: ISSN: 0953-816X
CoNE: https://pure.mpg.de/cone/journals/resource/954925575988