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

Fingerprint

Fragile X Mental Retardation Protein
Protein Phosphatase 2
Metabotropic Glutamate Receptors
Phosphorylation
TOR Serine-Threonine Kinases
Fragile X Syndrome
RNA-Binding Proteins
Phosphoprotein Phosphatases
Protein Biosynthesis
Dendrites
Intellectual Disability
Neurons

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

FMRP phosphorylation reveals an immediate-early signaling pathway triggered by group I mGluR and mediated by PP2A. / Narayanan, Usha; Nalavadi, Vijayalaxmi; Nakamoto, Mika; Pallas, David C.; Ceman, Stephanie; Bassell, Gary J.; Warren, Stephen T.

In: Journal of Neuroscience, Vol. 27, No. 52, 26.12.2007, p. 14349-14357.

Research output: Contribution to journalArticle

Narayanan, Usha ; Nalavadi, Vijayalaxmi ; Nakamoto, Mika ; Pallas, David C. ; Ceman, Stephanie ; Bassell, Gary J. ; Warren, Stephen T. / FMRP phosphorylation reveals an immediate-early signaling pathway triggered by group I mGluR and mediated by PP2A. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 52. pp. 14349-14357.
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AU - Nalavadi, Vijayalaxmi

AU - Nakamoto, Mika

AU - Pallas, David C.

AU - Ceman, Stephanie

AU - Bassell, Gary J.

AU - Warren, Stephen T.

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