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Brief Communications

Dephosphorylation-Induced Ubiquitination and Degradation of FMRP in Dendrites: A Role in Immediate Early mGluR-Stimulated Translation

Vijayalaxmi C. Nalavadi, Ravi S. Muddashetty, Christina Gross and Gary J. Bassell
Journal of Neuroscience 22 February 2012, 32 (8) 2582-2587; DOI: https://doi.org/10.1523/JNEUROSCI.5057-11.2012
Vijayalaxmi C. Nalavadi
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Ravi S. Muddashetty
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Christina Gross
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Gary J. Bassell
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Abstract

Fragile X syndrome is caused by the loss of fragile X mental retardation protein (FMRP), which represses and reversibly regulates the translation of a subset of mRNAs in dendrites. Protein synthesis can be rapidly stimulated by mGluR-induced and protein phosphatase 2a (PP2A)-mediated dephosphorylation of FMRP, which is coupled to the dissociation of FMRP and target mRNAs from miRNA-induced silencing complexes. Here, we report the rapid ubiquitination and ubiquitin proteasome system (UPS)-mediated degradation of FMRP in dendrites upon DHPG (3,5-dihydroxyphenylglycine) stimulation in cultured rat neurons. Using inhibitors to PP2A and FMRP phosphomutants, degradation of FMRP was observed to depend on its prior dephosphorylation. Translational induction of an FMRP target, postsynaptic density-95 mRNA, required both PP2A and UPS. Thus, control of FMRP levels at the synapse by dephosphorylation-induced and UPS-mediated degradation provides a mode to regulate protein synthesis.

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The Journal of Neuroscience: 32 (8)
Journal of Neuroscience
Vol. 32, Issue 8
22 Feb 2012
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Dephosphorylation-Induced Ubiquitination and Degradation of FMRP in Dendrites: A Role in Immediate Early mGluR-Stimulated Translation
Vijayalaxmi C. Nalavadi, Ravi S. Muddashetty, Christina Gross, Gary J. Bassell
Journal of Neuroscience 22 February 2012, 32 (8) 2582-2587; DOI: 10.1523/JNEUROSCI.5057-11.2012

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Dephosphorylation-Induced Ubiquitination and Degradation of FMRP in Dendrites: A Role in Immediate Early mGluR-Stimulated Translation
Vijayalaxmi C. Nalavadi, Ravi S. Muddashetty, Christina Gross, Gary J. Bassell
Journal of Neuroscience 22 February 2012, 32 (8) 2582-2587; DOI: 10.1523/JNEUROSCI.5057-11.2012
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