Diffusion and Not Active Transport Underlies and Limits ERK1/2 Synapse-to-Nucleus Signaling in Hippocampal Neurons*
Diffusion and Not Active Transport Underlies and Limits ERK1/2 Synapse-to-Nucleus Signaling in Hippocampal Neurons*
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DOI：
10.1074/jbc.m701448200
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发表时间：
2007-10
影响因子：
4.8
通讯作者：
J. Simon Wiegert;C. P. Bengtson;H. Bading
中科院分区：
文献类型：
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作者：
J. Simon Wiegert;C. P. Bengtson;H. Bading
从突触和树突到细胞核的信号传播对于神经系统中持久的适应性变化至关重要。ERK-MAPK通路可以将神经元活动和细胞表面受体活化与基因转录的调节联系起来，并且通常被认为是晚期可塑性和学习中突触-核通讯的主要介质。然而，ERK 1/2在树突中的运输和在神经元中的核转位的潜在机制仍有待确定，使得在突触处激活的ERK 1/2是否可以有助于核信号传导和转录调节尚不清楚。使用光漂白和光活化的荧光标记Dronpa的ERK 1和ERK 2，我们在这里表明，ERK 1/2易位到海马神经元的核是由N-甲基-d-天冬氨酸受体的刺激或TrkB刺激诱导的，显然是由易化扩散介导的。相比之下，树突内的ERK 1/2运输不受信号调节，而是由被动扩散介导。在树突内，ERK 1/2的局部激活池的范围非常有限，并且随着距离的增加呈指数衰减。这些结果表明，成功的信号传播到细胞核的ERK-MAPK途径依赖于细胞核的距离ERK 1/2激活的网站。在索马内或附近激活的ERK 1/2可以迅速到达细胞核以诱导基因表达，而在远端突触激活的ERK 1/2可能仅有助于局部信号传导。
The propagation of signals from synapses and dendrites to the nucleus is crucial for long lasting adaptive changes in the nervous system. The ERK-MAPK pathway can link neuronal activity and cell surface receptor activation to the regulation of gene transcription, and it is often considered the principal mediator of synapse-to-nucleus communication in late-phase plasticity and learning. However, the mechanisms underlying ERK1/2 trafficking in dendrites and nuclear translocation in neurons remain to be determined leaving it unclear whether ERK1/2 activated at the synapse can contribute to nuclear signaling and transcriptional regulation. Using the photobleachable and photoactivable fluorescent tag Dronpa on ERK1 and ERK2, we show here that ERK1/2 translocation to the nucleus of hippocampal neurons is induced by the stimulation of N-methyl-d-aspartate receptors or TrkB stimulation and is apparently mediated by facilitated diffusion. In contrast, ERK1/2 trafficking within dendrites is not signal-regulated and is mediated by passive diffusion. Within dendrites, the reach of a locally activated pool of ERK1/2 is very limited and follows an exponential decay with distance. These results indicate that successful signal propagation to the nucleus by the ERK-MAPK pathway depends on the distance of the nucleus from the site of ERK1/2 activation. ERK1/2 activated within or near the soma may rapidly reach the nucleus to induce gene expression, whereas ERK1/2 activated at distal synapses may only contribute to local signaling.