Signaling from synapse to nucleus: Postsynaptic CREB phosphorylation during multiple forms of hippocampal synaptic plasticity
Signaling from synapse to nucleus: Postsynaptic CREB phosphorylation during multiple forms of hippocampal synaptic plasticity
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DOI：
10.1016/s0896-6273(00)80026-4
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发表时间：
1996-01-01
期刊：
影响因子：
16.2
通讯作者：
Tsien, RW
中科院分区：
文献类型：
--
作者：
Deisseroth, K;Bito, H;Tsien, RW
转录因子CREB的磷酸化被认为在长期记忆的过程中是重要的。目前尚不清楚CREB磷酸化是否可以携带突触强度变化信号的信息，CREB通路在接受或提供突触输入的神经元中是否同样被激活，以及突触-核通信是如何介导的。我们发现Ca2+依赖的核CREB磷酸化被突触刺激迅速唤起，包括但不限于那些诱导突触强度增强和抑制的刺激。与之形成鲜明对比的是，单独的高频动作电位触发未能触发CREB磷酸化。Ca2+进入位点下方的膜下Ca2+传感器的激活对于通过钙调蛋白和Ca2+/钙调蛋白依赖性蛋白激酶触发核CREB磷酸化至关重要。
Phosphorylation of the transcription factor CREB is thought to be important in processes underlying long-term memory. It is unclear whether CREB phosphorylation can carry information about the sign of changes in synaptic strength, whether CREB pathways are equally activated in neurons receiving or providing synaptic input, or how synapse-to-nucleus communication is mediated. We found that Ca2+-dependent nuclear CREB phosphorylation was rapidly evoked by synaptic stimuli including, but not limited to, those that induced potentiation and depression of synaptic strength. In striking contrast, high frequency action potential firing alone failed to trigger CREB phosphorylation. Activation of a submembranous Ca2+ sensor, just beneath sites of Ca2+ entry, appears critical for triggering nuclear CREB phosphorylation via calmodulin and a Ca2+/calmodulin-dependent protein kinase.