Long-lasting behavioral responses to stress involve a direct interaction of glucocorticoid receptors with ERK1/2-MSK1-Elk-1 signaling

M Gutierrez-Mecinas, AF Trollope, A Collins, H Morfett, SA Hesketh, F Kersante, JMHM Reul

Research output: Contribution to journalArticle (Academic Journal)peer-review

99 Citations (Scopus)

Abstract

Stressful events are known to have a long-term impact on future behavioral stress responses. Previous studies suggested that both glucocorticoid hormones and glutamate acting via glucocorticoid receptors (GRs) and N-methyl D-aspartate (NMDA) receptors, respectively, are of critical importance for the consolidation of these long-lasting behavioral responses at the dentate gyrus, the gateway of the hippocampal formation. We found that an acute psychologically stressful event resulted in ERK1/2 phosphorylation (pERK1/2), which within 15 min led to the activation of the nuclear kinases MSK1 and Elk-1 in granule neurons of the dentate gyrus. Next, MSK1 and Elk-1 activation evoked serine-10 phosphorylation and lysine-14 acetylation in histone H3, resulting in the induction of the neuroplasticity-associated immediate-early genes c-Fos and Egr-1 in these neurons. The pERK1/2-mediated activation of MSK1 and Elk-1 required a rapid protein–protein interaction between pERK1/2 and activated GRs. This is a unique nongenomic mechanism of glucocorticoid hormone action in dentate gyrus granule neurons on long-lasting behavioral responses to stress involving direct cross-talk of GRs with ERK1/2–MSK1–Elk-1 signaling to the nucleus.
Translated title of the contributionLong-lasting behavioral responses to stress involve a direct interaction of glucocorticoid receptors with ERK1/2-MSK1-Elk-1 signaling
Original languageEnglish
Pages (from-to)13806 - 13811
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number33
Early online date1 Aug 2011
DOIs
Publication statusPublished - 16 Aug 2011

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