FMRP phosphorylation reveals an immediate-early signaling pathway triggered by group I mGluR and mediated by PP2A

Usha Narayanan, Vijayalaxmi Nalavadi, Mika Nakamoto, David C. Pallas, Stephanie Ceman, Gary J. Bassell, Stephen T. Warren

Research output: Contribution to journalArticle

Abstract

Fragile X syndrome is a common form of inherited mental retardation and is caused by loss of fragile X mental retardation protein (FMRP), a selective RNA-binding protein that influences the translation of target messages. Here, we identify protein phosphatase 2A (PP2A) as an FMRP phosphatase and report rapid FMRP dephosphorylation after immediate group I metabotropic glutamate receptor (mGluR) stimulation (<1 min) in neurons caused by enhanced PP2A enzymatic activity. In contrast, extended mGluR activation (1-5 min) resulted in mammalian target of rapamycin (mTOR)-mediated PP2A suppression and FMRP rephosphorylation. These activity-dependent changes in FMRP phosphorylation were also observed in dendrites and showed a temporal correlation with the translational profile of select FMRP target transcripts. Collectively, these data reveal an immediate-early signaling pathway linking group I mGluR activity to rapid FMRP phosphorylation dynamics mediated by mTOR and PP2A.

Original languageEnglish (US)
Pages (from-to)14349-14357
Number of pages9
JournalJournal of Neuroscience
Volume27
Issue number52
DOIs
StatePublished - Dec 26 2007

Keywords

  • FMRP
  • Fragile X
  • PP2A
  • Phosphorylation
  • Synaptic plasticity
  • mGluR

ASJC Scopus subject areas

  • Neuroscience(all)

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