MSK1 regulates transcriptional induction of Arc/Arg3.1 in response to neurotrophins

Christopher Hunter, Judit Remenyi, Sonia A. L. Corrêa, Lucia Privitera, Kathleen Reyskens, Kirsty Martin, Rachel Toth, Bruno Frenguelli, John Arthur (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)
244 Downloads (Pure)

Abstract

The immediate early gene activity-regulated cytoskeletal protein (Arc)/Arg3.1 and the neurotrophin brain-derived neurotrophic factor (BDNF) play important roles in synaptic plasticity and learning and memory in the mammalian brain. However, the mechanisms by which BDNF regulates the expression of Arc/Arg3.1 are unclear. In this study, we show that BDNF acts via the ERK1/2 pathway to activate the nuclear kinase mitogen- and stress-activated protein kinase 1 (MSK1). MSK1 then induces Arc/Arg3.1 expression via the phosphorylation of histone H3 at the Arc/Arg3.1 promoter. MSK1 can also phosphorylate the transcription factor cyclic-AMP response element-binding protein (CREB) on Ser133. However, this is not required for BDNF-induced Arc.Arg3.1 transcription as a Ser133Ala knockin mutation had no effect on Arc/Arg3.1 induction. In parallel, ERK1/2 directly activates Arc/Arg3.1 mRNA transcription via at least one serum response element on the promoter, which bind a complex of the Serum Response Factor (SRF) and a Ternary Complex Factor (TCF).
Original languageEnglish
Pages (from-to)821-834
Number of pages14
JournalFEBS Open Bio
Volume7
Issue number6
Early online date20 Apr 2017
DOIs
Publication statusPublished - 5 Jun 2017

Keywords

  • Arc-Arg3.1
  • BDNF
  • CREB
  • glutamate
  • histone H3
  • MSK1
  • neurotrophins
  • NMDA

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