FXR2P Exerts a Positive Translational Control and Is Required for the Activity-Dependent Increase of PSD95 Expression
FXR2P Exerts a Positive Translational Control and Is Required for the Activity-Dependent Increase of PSD95 Expression
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DOI：
10.1523/jneurosci.4800-14.2015
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发表时间：
2015-06-24
影响因子：
5.3
通讯作者：
Bagni, Claudia
中科院分区：
文献类型：
--
作者：
Fernandez, Esperanza;Li, Ka Wan;Bagni, Claudia
在大脑中，特定的 RNA 结合蛋白 (RBP) 与局部 mRNA 相关，并作为突触蛋白质合成的调节剂，对神经元活动发挥间接控制作用。因此，脆性 X 型智力迟钝蛋白 (FMRP) 调节支架突触后密度蛋白 PSD95 的表达，但控制模式似乎与其他 FMRP 靶 mRNA 不同。在这里，我们发现脆性 X 智力低下相关蛋白 2 (FXR2P) 与 FMRP 协同结合小鼠 PSD95/Dlg4 mRNA 的 3'-UTR。 FXR2P 的缺失会导致海马中 PSD95/Dlg4 mRNA 的翻译减少，这意味着 FXR2P 作为翻译激活剂的作用。值得注意的是，在缺乏 Fxr2 的神经元中，mGluR 依赖性 PSD95 合成增加被消除。总之，这些发现表明 FMRP 和 FXR2P 对 PSD95/Dlg4 mRNA 的协调调节，最终影响其在突触活动期间的微调。
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.