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

Thabat Khatib, Andrew Whiting, David R Chisholm, Christopher Redfern, Berndt Muller, Peter McCaffery (Corresponding Author)

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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.
Original languageEnglish
Pages (from-to)7074-7084
Number of pages11
JournalMolecular Neurobiology
Volume56
Issue number10
Early online date10 Apr 2019
DOIs
Publication statusPublished - Oct 2019

Keywords

  • RAR
  • retinoic acid
  • GluR1
  • non-genomic
  • Non-genomic
  • Retinoic acid
  • HUMAN NEUROBLASTOMA-CELLS
  • RNA GRANULES
  • ACTIVATION
  • ANALOGS
  • RAR-ALPHA
  • DIFFERENTIATED SH-SY5Y
  • DERIVATIVES
  • EXPRESSION
  • BRAIN
  • PLASTICITY

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