Visual experience regulates transient expression and dendritic localization of Fragile X mental retardation protein
Visual experience regulates transient expression and dendritic localization of Fragile X mental retardation protein
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DOI：
10.1523/jneurosci.2185-04.2004
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发表时间：
2004-11-24
影响因子：
5.3
通讯作者：
Fallon, JR
中科院分区：
文献类型：
--
作者：
Gabel, LA;Won, S;Fallon, JR
脆性X综合征是遗传性智力低下的最常见形式，由脆性X智力低下蛋白（FMRP）的功能丧失引起。FMRP是一种RNA结合蛋白，被认为在蛋白质合成依赖性突触可塑性中起关键作用。FMRP表达调控本身也可能是这一过程中的重要控制点。在这里，我们使用黑暗饲养/光照暴露的大鼠来确定经验在调节视觉皮层中FMRP水平中的作用。我们发现，FMRP水平增加的视皮层神经元的细胞体和树突后，短短15分钟的曝光。值得注意的是，这些神经元中的FMRP表达在30分钟的光照下恢复到基线水平。这些变化是转录后的，因为FMR 1 mRNA水平在这段时间内保持恒定。在从光暴露动物的视觉皮层制备的突触组分中也观察到FMRP水平的短暂增加。与此相反，α-钙/钙调蛋白依赖性激酶II的表达在这些条件下表现出持续上调。最后，FMRP表达的增加被NMDA受体阻断剂抑制。这种紧密的时空调节表明，FMRP在经验依赖性突触可塑性的一个独特时代中起着动态作用。
Fragile X syndrome is the most common form of inherited mental retardation and is caused by the loss of function of the Fragile X mental retardation protein (FMRP). FMRP is an RNA binding protein thought to play a key role in protein synthesis-dependent synaptic plasticity. The regulation of FMRP expression itself is also likely to be an important control point in this process. Here we used dark-reared/light-exposed rats to determine the role of experience in regulating FMRP levels in the visual cortex. We find that FMRP levels increase in the cell bodies and dendrites of visual cortical neurons after as little as 15 min of light exposure. Remarkably, FMRP expression in these neurons returns to baseline levels by 30 min of light exposure. These changes were post-transcriptional because the FMR1 mRNA levels remained constant over this time period. A transient increase in FMRP levels was also observed in synaptic fractions prepared from visual cortices of light-exposed animals. In contrast, alpha-calcium/calmodulin-dependent kinase II expression showed a sustained upregulation under these conditions. Finally, the increase in FMRP expression was inhibited by blockade of NMDA receptors. This tight temporal-spatial regulation suggests that FMRP plays a dynamic role in a distinct epoch of experience-dependent synaptic plasticity.