Altered mRNA transport, docking, and protein translation in neurons lacking fragile X mental retardation protein
Altered mRNA transport, docking, and protein translation in neurons lacking fragile X mental retardation protein
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DOI：
10.1073/pnas.1010564107
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发表时间：
2010-08-31
影响因子：
11.1
通讯作者：
Greenough, William T.
中科院分区：
文献类型：
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作者：
Kao, Der-I;Aldridge, Georgina M.;Greenough, William T.
脆性X综合征是由功能性脆性X智力低下蛋白（FMRP），一种RNA结合蛋白的缺乏引起的。fmr 1基因敲除小鼠蛋白质合成异常的分子机制与FMRP在mRNA转运、递送和局部蛋白质合成中的作用密切相关。我们发现，GFP标记的Fmr 1和CaMKII α mRNA进行减速运动后，0-40分钟组I mGluR刺激，后来恢复在40-60分钟。然后，我们研究神经元刺激后与FMRP相关的mRNA的靶向。我们发现，FMRP的合成密切邻近刺激mGluR 5受体。此外，在WT神经元中，响应于I组mGluR刺激，CaMKII α mRNA可以在10分钟内在树突棘中递送和翻译，而KO神经元未能显示出这种响应。这些数据表明，FMRP可以介导空间mRNA的传递，以响应突触刺激的局部蛋白质合成。
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 CaMKII alpha 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, CaMKII alpha 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.