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Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
Published on: May 19, 2016
FMRP phosphorylation reveals an immediate-early signaling pathway triggered by group I mGluR and mediated by PP2A
Usha Narayanan1, Vijayalaxmi Nalavadi, Mika Nakamoto
1Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
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.
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