RT Journal Article
SR Electronic
T1 FMRP Phosphorylation Reveals an Immediate-Early Signaling Pathway Triggered by Group I mGluR and Mediated by PP2A
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 14349
OP 14357
DO 10.1523/JNEUROSCI.2969-07.2007
VO 27
IS 52
A1 Narayanan, Usha
A1 Nalavadi, Vijayalaxmi
A1 Nakamoto, Mika
A1 Pallas, David C.
A1 Ceman, Stephanie
A1 Bassell, Gary J.
A1 Warren, Stephen T.
YR 2007
UL http://www.jneurosci.org/content/27/52/14349.abstract
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.