RNA editing produces glycine receptor α3P185L, resulting in high agonist potency

J C Meier; C Henneberger; I Melnick; C Racca; Robert J Harvey; U Heinemann; V Schmieden; R Grantyn

doi:10.1038/nn1467

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RNA editing produces glycine receptor α3P185L, resulting in high agonist potency

Journal article

Peer reviewed

RNA editing produces glycine receptor α3P185L, resulting in high agonist potency

J C Meier, C Henneberger, I Melnick, C Racca, Robert J Harvey, U Heinemann, V Schmieden and R Grantyn

Nature Neuroscience, Vol.8(6), pp.736-744

2005

DOI: https://doi.org/10.1038/nn1467

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Abstract

cycloheximide

cytidine

dactinomycin

glycine

glycine receptor

glycine receptor alpha3

messenger RNA

unclassified drug

zebularine

chloride channel

enzyme inhibitor

glycine receptor alpha3 subunit

isoprotein

protein synthesis inhibitor

animal c

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 μM). Searching for the molecular basis of this phenomenon, we identified a new GlyR isoform. GlyRα3 P185L, a result of cytidine 554 deamination, confers high glycine sensitivity (EC50 ∼5 μM) to neurons and thereby promotes the generation of sustained chloride conductances associated with tonic inhibition. The level of GlyRα3-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 GlyRα3 P185L is thus likely to be part of a post-transcriptional adaptive mechanism in neurons with enhanced excitability. © 2005 Nature Publishing Group.

Details

Title: RNA editing produces glycine receptor α3P185L, resulting in high agonist potency
Authors: J C Meier (Author) - Charite University Medicine, Germany
C Henneberger (Author) - Charite University Medicine, Germany
I Melnick (Author) - Charite University Medicine, Germany
C Racca (Author) - University of Leeds, United Kingdom
Robert J Harvey (Author) - University College London, United Kingdom
U Heinemann (Author) - Charite University Medicine, Germany
V Schmieden (Author) - Charite University Medicine, Germany
R Grantyn (Author) - Charite University Medicine, Germany
Publication details: Nature Neuroscience, Vol.8(6), pp.736-744
Publisher: Nature Publishing Group
Date published: 2005
DOI: 10.1038/nn1467
ISSN: 1097-6256
Organisation Unit: School of Health; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99450516102621
Output Type: Journal article

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Web Of Science research areas: Neurosciences

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