Fragile X mental retardation protein is necessary for neurotransmitter-activated protein translation at synapses
Fragile X mental retardation protein is necessary for neurotransmitter-activated protein translation at synapses
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DOI：
10.1073/pnas.0407533101
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发表时间：
2004-12-14
影响因子：
11.1
通讯作者：
Greenough, WT
中科院分区：
文献类型：
--
作者：
Weiler, IJ;Spangler, CC;Greenough, WT
脆性 X 型智力低下是由于缺乏由 FMR1 基因编码的 RNA 结合蛋白脆性 X 型智力低下蛋白 (FMRP) 引起的。越来越多的证据表明 FMRP 调节某些 mRNA 的运输和翻译。我们研究了 fmr1 敲除小鼠中神经递质激活的突触蛋白合成。来自基因敲除小鼠的突触神经体没有表现出加速的多核糖体组装或蛋白质合成，而野生型小鼠在刺激 I 组代谢型谷氨酸受体时会出现这种情况。蛋白激酶 C 的直接激活在敲除小鼠中没有得到补偿，表明 FMRP 依赖性步骤沿着信号通路进一步进行。年轻的基因敲除小鼠的视觉皮层中含有多核糖体的树突棘突触的比例低于野生型小鼠的皮层，在体内证实了这一发现。这种由神经递质控制的特定蛋白质的快速局部翻译的缺陷可能导致脆性 X 综合征患者观察到的形态和功能异常。
Fragile X mental retardation is caused by absence of the RNA-binding protein fragile X mental retardation protein (FMRP), encoded by the FMR1 gene. There is increasing evidence that FMRP regulates transport and modulates translation of some mRNAs. We studied neurotransmitter-activated synaptic protein synthesis in fmr1-knockout mice. Synaptoneurosomes from knockout mice did not manifest accelerated polyribosome assembly or protein synthesis as it occurs in wild-type mice upon stimulation of group I metabotropic glutamate receptors. Direct activation of protein kinase C did not compensate in the knockout mouse, indicating that the FMRP-dependent step is further along the signaling pathway. Visual cortices of young knockout mice exhibited a lower proportion of dendritic spine synapses containing polyribosomes than did the cortices of wild-type mice, corroborating this finding in vivo. This deficit in rapid neurotransmitter-controlled local translation of specific proteins may contribute to morphological and functional abnormalities observed in patients with fragile X syndrome.