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RNA editing produces glycine receptor alpha3(P185L), resulting in high agonist potency

Item Type:Article
Title:RNA editing produces glycine receptor alpha3(P185L), resulting in high agonist potency
Creators Name:Meier, J.C. and Henneberger, C. and Melnick, I. and Racca, C. and Harvey, R.J. and Heinemann, U. and Schmieden, V. and Grantyn, R.
Abstract:The function of supramedullary glycine receptors (GlyRs) is still unclear. Using Wistar rat collicular slices, we demonstrate GlyR-mediated inhibition of spike discharge elicited by low glycine (10 microM). Searching for the molecular basis of this phenomenon, we identified a new GlyR isoform. GlyR alpha3(P185L), a result of cytidine 554 deamination, confers high glycine sensitivity (EC50 approximately 5 microM) to neurons and thereby promotes the generation of sustained chloride conductances associated with tonic inhibition. The level of GlyR alpha3-C554U RNA editing is sensitive to experimentally induced brain lesion, inhibition of cytidine deamination by zebularine and inhibition of mRNA transcription by actinomycin D, but not to blockade of protein synthesis by cycloheximide. Conditional regulation of GlyR alpha3(P185L) is thus likely to be part of a post-transcriptional adaptive mechanism in neurons with enhanced excitability.
Keywords:Action Potentials, Amino Acid Sequence, Chloride Channels, Cytidine, Deamination, Enzyme Inhibitors, Gene Expression Regulation, Glycine, Molecular Sequence Data, Neural Inhibition, Neurons, Organ Culture Techniques, Patch-Clamp Techniques, Protein Isoforms, Post-Translational Protein Processing, Protein Synthesis Inhibitors, RNA Editing, Messenger RNA, Glycine Receptors, Superior Colliculi, Animals, Rats
Source:Nature Neuroscience
ISSN:1097-6256
Publisher:Nature Publishing Group (U.S.A.)
Volume:8
Number:6
Page Range:736-744
Date:June 2005
Official Publication:https://doi.org/10.1038/nn1467
PubMed:View item in PubMed

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