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A Bioluminescence Reporter Assay for Retinoic Acid Control of Translation of the GluR1 Subunit of the AMPA Glutamate Receptor

Khatib, Thabat; Whiting, Andrew; Chisholm, David R.; Redfern, Christopher; Müller, Berndt; McCaffery, Peter

A Bioluminescence Reporter Assay for Retinoic Acid Control of Translation of the GluR1 Subunit of the AMPA Glutamate Receptor Thumbnail


Authors

Thabat Khatib

Christopher Redfern

Berndt Müller

Peter McCaffery



Abstract

Retinoic acid (RA) regulates numerous aspects of central nervous system function through modulation of gene transcription via retinoic acid receptors (RARs). However, RA has important roles independent of gene transcription (non-genomic actions) and in the brain a crucial regulator of homeostatic plasticity is RAR control of glutamate receptor subunit 1 (GluR1) translation. An assay to quantify RAR regulation of GluR1 translation would be beneficial both to study the molecular components regulating this system and screen drugs that influence this critical mechanism for learning and memory in the brain. A bioluminescence reporter assay was developed that expresses firefly luciferase under the control of the GluR1 5′ untranslated region bound by RAR. This assay was introduced into SH-SY5Y cells and used to demonstrate the role of RARα in RA regulation of GluR1 translation. A screen of synthetic RAR and RXR ligands indicated that only a subset of these ligands activated GluR1 translation. The results demonstrate the practicality of this assay to explore the contribution of RARα to this pathway and that the capacity of RAR ligands to activate translation is a quality restricted to a limited number of compounds, with implications for their RAR selectivity and potentially their specificity in drug use.

Citation

Khatib, T., Whiting, A., Chisholm, D. R., Redfern, C., Müller, B., & McCaffery, P. (2019). A Bioluminescence Reporter Assay for Retinoic Acid Control of Translation of the GluR1 Subunit of the AMPA Glutamate Receptor. Molecular Neurobiology, 56(10), 7074-7084. https://doi.org/10.1007/s12035-019-1571-9

Journal Article Type Article
Acceptance Date Mar 20, 2019
Online Publication Date Apr 10, 2019
Publication Date Oct 31, 2019
Deposit Date May 9, 2019
Publicly Available Date May 9, 2019
Journal Molecular Neurobiology
Print ISSN 0893-7648
Electronic ISSN 1559-1182
Publisher Springer
Peer Reviewed Peer Reviewed
Volume 56
Issue 10
Pages 7074-7084
DOI https://doi.org/10.1007/s12035-019-1571-9

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
Advance online version © The Author(s) 2019.
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.






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