Translocation of calmodulin to the nucleus supports CREB phosphorylation in hippocampal neurons
Translocation of calmodulin to the nucleus supports CREB phosphorylation in hippocampal neurons
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DOI：
10.1038/32448
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发表时间：
1998-03-12
期刊：
影响因子：
64.8
通讯作者：
Tsien, RW
中科院分区：
文献类型：
--
作者：
Deisseroth, K;Heist, EK;Tsien, RW
转录因子CREB的激活被认为在几种动物物种的长期记忆形成中是重要的（1-3）。CREB的133位丝氨酸残基的磷酸化对于CREB 4的活化至关重要。当海马神经元中短暂的突触活动驱动时，这种磷酸化是快速的（5），它是由细胞膜附近钙离子浓度的高度局部升高（5）引发的，但在被称为CaMK IV的特异性钙调蛋白依赖性激酶的激活中达到高潮（参考文献7），其组成性地存在于神经元核中（7，8）。目前还不清楚信号是如何从突触传递到细胞核的，我们在这里表明，短暂的活动爆发会引起迅速的反应。（类似于1分钟）钙调蛋白从细胞质转运到细胞核，并且这种转运对于CREB的快速磷酸化非常重要，某些Ca 2+进入系统（L型Ca 2+通道和NMDA受体）能够引起钙调蛋白的动员，而其他（N型和P/Q型Ca 2+通道）则不能。钙调素的这种易位提供了一种细胞通讯的形式，它将局部Ca 2+信号传导的特异性与远距离产生作用的能力相结合。
Activation of the transcription factor CREB is thought to be important in the formation of long-term memory in several animal species(1-3). The phosphorylation of a serine residue at position 133 of CREB is critical for activation of CREB4. This phosphorylation is rapid when driven by brief synaptic activity in hippocampal neurons(5), It is initiated by a highly local, rise in calcium ion concentration(5) near the cell membrane, but culminates in the activation of a specific calmodulin-dependent kinase known as CaMK IV (ref. 7), which is constitutively present in the neuronal nucleus(7,8). It is unclear how the signal is conveyed from the synapse to the nucleus, We show here that brief bursts of activity cause a swift (similar to 1 min) translocation of calmodulin from the cytoplasm to the nucleus, and that this translocation is important for the rapid phosphorylation of CREB, Certain Ca2+ entry systems (L-type Ca2+ channels and NMDA receptors) are able to cause mobilization of calmodulin, whereas others (N- and P/Q-type Ca2+ channels) are not. This translocation of calmodulin provides a form of cellular communication that combines the specificity of local Ca2+ signalling with the ability to produce action at a distance.