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          Institute: MPI für medizinische Forschung     Collection: Abteilung Zellphysiologie     Display Documents



ID: 23276.0, MPI für medizinische Forschung / Abteilung Zellphysiologie
Genetic manipulation of key determinants of ion flow in glutamate receptor channels in the mouse
Translation of Title:Genetic manipulation of key determinants of ion flow in glutamate receptor channels in the mouse
Authors:Seeburg, Peter H.; Single, Frank N.; Kuner, Thomas; Higuchi, Miyoko; Sprengel, Rolf
Language:English
Date of Publication (YYYY-MM-DD):2001-07-13
Title of Journal:Brain Research
Journal Abbrev.:Brain Res.
Volume:907
Issue / Number:1
Start Page:233
End Page:243
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Glutamate receptor channels are built around an ancient pore loop structure which defines the inner channel environment and which is connected to structures for channel gating. This pore loop, which corresponds to the M2 region of the receptor subunits, enters the lipid bilayer from the intracellular side in an alpha-helical configuration, then kinks to form a random coil and exits the lipid bilayer at the intracellular side. The narrow constriction of the channel is formed by amino acid residues that occupy a position shortly after the end of the alpha-helical part of M2. These residues determine ion selectivity and conductance properties of the glutamate-gated channel. The critical residues are asparagines for NMDA receptor subunits and glutamine or arginine for AMPA and kainate receptor subunits. Presence of arginine in the critical channel position of AMPA and kainate receptors is controlled by site-selective RNA editing. To study the importance of these critical channel residues in the mouse, we introduced codon changes in the endogenous genes for NMDA and AMPA receptor subunits. Our results show that changes in the critical channel position are not tolerated, but lead to early death. Therefore, the impact on adult synaptic function and plasticity by glutamate receptor channels with changed ion selectivity and conductance needs to be addressed by conditional expression of the mutant receptors.
Free Keywords:Neurotransmitters, modulators, transporters and receptors, Excitatory amino acid receptors: ligand-gated ion channels; AMPA and NMDA receptors; Gene targeting in the mouse; Insertional gene silencing; RNA editing; Adenosine deaminases acting on RNA (ADARs)
External Publication Status:published
Document Type:Article
Communicated by:Wulf Kaiser
Affiliations:MPI für medizinische Forschung/Abteilung Zellphysiologie/
MPI für medizinische Forschung/Abteilung Molekulare Neurobiologie/
Identifiers:URI:http://www.sciencedirect.com/science?_ob=ArticleUR... [Full text]
URI:http://www.sciencedirect.com/science?_ob=ArticleUR... [Abstract]
URI:http://www.sciencedirect.com/science?_ob=MImg&_ima... [Fulltext PDF]
DOI:10.1016/S0006-8993(01)02445-3
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