FXR2P Exerts a Positive Translational Control and Is Required for the Activity-Dependent Increase of PSD95 Expression
Copyright policy )FXR2P Exerts a Positive Translational Control and Is Required for the Activity-Dependent Increase of PSD95 Expression
In brain, specific RNA-binding proteins (RBPs) associate with localized mRNAs and function as regulators of protein synthesis at synapses exerting an indirect control on neuronal activity. Thus, the Fragile X Mental Retardation protein (FMRP) regulates expression of the scaffolding postsynaptic density protein PSD95, but the mode of control appears to be different from other FMRP target mRNAs. Here, we show that the fragile X mental retardation-related protein 2 (FXR2P) cooperates with FMRP in binding to the 3'-UTR of mouse PSD95/Dlg4 mRNA. Absence of FXR2P leads to decreased translation of PSD95/Dlg4 mRNA in the hippocampus, implying a role for FXR2P as translation activator. Remarkably, mGluR-dependent increase of PSD95 synthesis is abolished in neurons lacking Fxr2. Together, these findings show a coordinated regulation of PSD95/Dlg4 mRNA by FMRP and FXR2P that ultimately affects its fine-tuning during synaptic activity.
- University of Rome Tor Vergata Italy
- University of Amsterdam Netherlands
- Vrije Universiteit Amsterdam Netherlands
- Amsterdam Neuroscience Netherlands
- Katholieke Universiteit Leuven Belgium
570, mRNA translation, FXR2P, Knockout, Blotting, Western, Inbred C57BL, Mice, 616, Settore BIO/13 - BIOLOGIA APPLICATA, Animals, Immunoprecipitation, Membrane Protein, Mice, Knockout, Neurons, Neuronal Plasticity, Protein Biosynthesi, Animal, Blotting, PSD95, Membrane Proteins, RNA-Binding Proteins, Neuron, RNA binding protein, Guanylate Kinase, Immunohistochemistry, Mice, Inbred C57BL, Gene Expression Regulation, Protein Biosynthesis, FMRP, FMRP; FXR2P; PSD95; RNA binding proteins; mRNA translation; Animals; Blotting, Western; Gene Expression Regulation; Guanylate Kinase; Immunohistochemistry; Immunoprecipitation; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Neuronal Plasticity; Neurons; Protein Biosynthesis; RNA-Binding Proteins, Western, Disks Large Homolog 4 Protein, Guanylate Kinases
570, mRNA translation, FXR2P, Knockout, Blotting, Western, Inbred C57BL, Mice, 616, Settore BIO/13 - BIOLOGIA APPLICATA, Animals, Immunoprecipitation, Membrane Protein, Mice, Knockout, Neurons, Neuronal Plasticity, Protein Biosynthesi, Animal, Blotting, PSD95, Membrane Proteins, RNA-Binding Proteins, Neuron, RNA binding protein, Guanylate Kinase, Immunohistochemistry, Mice, Inbred C57BL, Gene Expression Regulation, Protein Biosynthesis, FMRP, FMRP; FXR2P; PSD95; RNA binding proteins; mRNA translation; Animals; Blotting, Western; Gene Expression Regulation; Guanylate Kinase; Immunohistochemistry; Immunoprecipitation; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Neuronal Plasticity; Neurons; Protein Biosynthesis; RNA-Binding Proteins, Western, Disks Large Homolog 4 Protein, Guanylate Kinases
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