Department of Cell and Developmental Biology, Beckman Institute, Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15601-6. doi: 10.1073/pnas.1010564107. Epub 2010 Aug 16.
Fragile X syndrome is caused by the absence of functional fragile X mental retardation protein (FMRP), an RNA binding protein. The molecular mechanism of aberrant protein synthesis in fmr1 KO mice is closely associated with the role of FMRP in mRNA transport, delivery, and local protein synthesis. We show that GFP-labeled Fmr1 and CaMKIIalpha mRNAs undergo decelerated motion at 0-40 min after group I mGluR stimulation, and later recover at 40-60 min. Then we investigate targeting of mRNAs associated with FMRP after neuronal stimulation. We find that FMRP is synthesized closely adjacent to stimulated mGluR5 receptors. Moreover, in WT neurons, CaMKIIalpha mRNA can be delivered and translated in dendritic spines within 10 min in response to group I mGluR stimulation, whereas KO neurons fail to show this response. These data suggest that FMRP can mediate spatial mRNA delivery for local protein synthesis in response to synaptic stimulation.
脆性 X 综合征是由功能性脆性 X 智力迟钝蛋白（FMRP）缺失引起的，FMRP 是一种 RNA 结合蛋白。fmr1 KO 小鼠中异常蛋白质合成的分子机制与 FMRP 在 mRNA 运输、传递和局部蛋白质合成中的作用密切相关。我们表明，在第 I 组 mGluR 刺激后 0-40 分钟，GFP 标记的 Fmr1 和 CaMKIIalpha mRNA 会经历减速运动，然后在 40-60 分钟恢复。然后，我们研究了神经元刺激后与 FMRP 相关的 mRNA 的靶向。我们发现 FMRP 与受刺激的 mGluR5 受体紧密相邻合成。此外，在 WT 神经元中，CaMKIIalpha mRNA 可以在第 I 组 mGluR 刺激后 10 分钟内被递送到树突棘中并进行翻译，而 KO 神经元则无法做出这种反应。这些数据表明，FMRP 可以介导空间 mRNA 传递，以响应突触刺激进行局部蛋白质合成。
