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

Gutirrèz-Mecinas, María, Trollope, Alexandra F., Collins, Andrew, Morfett, Hazel, Hesketh, Shirley A., Kersanté, Flavie, and Reul, Johannes M.H.M. (2011) Long-lasting behavioral responses to stress involve a direct interaction of glucocorticoid receptors with ERK1/2–MSK1–Elk-1 signaling. Proceedings of the National Academy of Sciences of the United States of America, 108 (33). pp. 13806-13811.

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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.

Item ID: 26845
Item Type: Article (Research - C1)
ISSN: 1091-6490
Keywords: corticosterone; chromatin; epigenetics; hippocampus; memory
Date Deposited: 20 May 2013 23:18
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060111 Signal Transduction @ 85%
06 BIOLOGICAL SCIENCES > 0604 Genetics > 060404 Epigenetics (incl Genome Methylation and Epigenomics) @ 5%
17 PSYCHOLOGY AND COGNITIVE SCIENCES > 1702 Cognitive Science > 170205 Neurocognitive Patterns and Neural Networks @ 10%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 70%
97 EXPANDING KNOWLEDGE > 970117 Expanding Knowledge in Psychology and Cognitive Sciences @ 30%
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