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Genomic and non-genomic pathways are both crucial for peak induction of neurite outgrowth by retinoids

Khatib, Thabat; Marini, Pietro; Nunna, Sudheer; Chisholm, David R.; Whiting, Andrew; Redfern, Christopher; Greig, Iain R.; McCaffery, Peter

Genomic and non-genomic pathways are both crucial for peak induction of neurite outgrowth by retinoids Thumbnail


Thabat Khatib

Pietro Marini

Sudheer Nunna

David R. Chisholm

Christopher Redfern

Iain R. Greig

Peter McCaffery


Retinoic acid (RA) is the active metabolite of vitamin A and essential for many physiological processes, particularly the induction of cell differentiation. In addition to regulating genomic transcriptional activity via RA receptors (RARs) and retinoid X receptors (RXRs), non-genomic mechanisms of RA have been described, including the regulation of ERK1/2 kinase phosphorylation, but are poorly characterised. In this study, we test the hypothesis that genomic and non-genomic mechanisms of RA are regulated independently with respect to the involvement of ligand-dependent RA receptors. A panel of 28 retinoids (compounds with vitamin A-like activity) showed a marked disparity in genomic (gene expression) versus non-genomic (ERK1/2 phosphorylation) assays. These results demonstrate that the capacity of a compound to activate gene transcription does not necessarily correlate with its ability to regulate a non-genomic activity such as ERK 1/2 phosphorylation. Furthermore, a neurite outgrowth assay indicated that retinoids that could only induce either genomic, or non-genomic activities, were not strong promoters of neurite outgrowth, and that activities with respect to both transcriptional regulation and ERK1/2 phosphorylation produced maximum neurite outgrowth. These results suggest that the development of effective retinoids for clinical use will depend on the selection of compounds which have maximal activity in non-genomic as well as genomic assays.


Khatib, T., Marini, P., Nunna, S., Chisholm, D. R., Whiting, A., Redfern, C., …McCaffery, P. (2019). Genomic and non-genomic pathways are both crucial for peak induction of neurite outgrowth by retinoids. Cell Communication and Signaling, 17(1), Article 40.

Journal Article Type Article
Acceptance Date Apr 9, 2019
Online Publication Date May 2, 2019
Publication Date May 2, 2019
Deposit Date May 9, 2019
Publicly Available Date May 9, 2019
Journal Cell Communication and Signaling
Publisher BioMed Central
Peer Reviewed Peer Reviewed
Volume 17
Issue 1
Article Number 40


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