NF-κB functions in synaptic signaling and behavior
NF-κB functions in synaptic signaling and behavior
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DOI：
10.1038/nn1110
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发表时间：
2003-10-01
影响因子：
25
通讯作者：
Baltimore, D
中科院分区：
文献类型：
--
作者：
Meffert, MK;Chang, JM;Baltimore, D
Ca 2+调控的基因转录对多种生理过程至关重要，包括与学习相关的适应性可塑性。我们发现，基础突触输入激活NF-κ B转录因子的途径需要钙/钙调蛋白依赖性激酶CaMKII和局部膜下钙离子升高。p65：p50 NF-kappaB形式选择性地定位于突触; p65缺陷小鼠没有可检测的突触NF-kappaB。激活的NF-κ B移动到细胞核，并可以直接将突触信号转化为改变的基因表达。缺乏p65的小鼠在径向臂迷宫的空间版本中显示出选择性学习缺陷。这些观察结果表明，突触刺激引起的成年神经元功能的长期变化可以通过NF-κ B核转位和基因激活来调节。
Ca2+-regulated gene transcription is essential to diverse physiological processes, including the adaptive plasticity associated with learning. We found that basal synaptic input activates the NF-kappaB transcription factor by a pathway requiring the Ca2+ /calmodulin-dependent kinase CaMKII and local submembranous Ca2+ elevation. The p65: p50 NF-kappaB form is selectively localized at synapses; p65-deficient mice have no detectable synaptic NF-kappaB. Activated NF-kappaB moves to the nucleus and could directly transmute synaptic signals into altered gene expression. Mice lacking p65 show a selective learning deficit in the spatial version of the radial arm maze. These observations suggest that long-term changes to adult neuronal function caused by synaptic stimulation can be regulated by NF-kappaB nuclear translocation and gene activation.