PT  - JOURNAL ARTICLE
AU  - Narayanan, Usha
AU  - Nalavadi, Vijayalaxmi
AU  - Nakamoto, Mika
AU  - Pallas, David C.
AU  - Ceman, Stephanie
AU  - Bassell, Gary J.
AU  - Warren, Stephen T.
TI  - FMRP Phosphorylation Reveals an Immediate-Early Signaling Pathway Triggered by Group I mGluR and Mediated by PP2A
AID  - 10.1523/JNEUROSCI.2969-07.2007
DP  - 2007 Dec 26
TA  - The Journal of Neuroscience
PG  - 14349--14357
VI  - 27
IP  - 52
4099  - http://www.jneurosci.org/content/27/52/14349.short
4100  - http://www.jneurosci.org/content/27/52/14349.full
SO  - J. Neurosci.2007 Dec 26; 27
AB  - 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.