Voltage-gated channels block nicotinic regulation of CREB phosphorylation and gene expression in neurons
Voltage-gated channels block nicotinic regulation of CREB phosphorylation and gene expression in neurons
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DOI：
10.1016/s0896-6273(01)00516-5
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发表时间：
2001-12-06
期刊：
影响因子：
16.2
通讯作者：
Berg, DK
中科院分区：
文献类型：
--
作者：
Chang, KT;Berg, DK
转录因子CREB的突触激活和下游基因表达通常依赖于电压门控钙通道辅助的钙内流。我们发现，烟碱信号，相反，激活CREB和基因表达睫状神经节神经元在文化和原位只有当电压门控通道是沉默的。烟碱反应需要钙内流和从内部储存释放，并通过CaMK和MAPK途径起作用以维持激活的CREB。电压门控通道最初动员CaMK激活CREB，但它们也使钙调神经磷酸酶和PP1在转录受到影响之前终止激活。L型电压门控通道主导结果并阻断烟碱信号对转录的影响。这证明了活性依赖性基因调控的一个新方面。
Synaptic activation of the transcription factor CREB and downstream gene expression usually depend on calcium influx aided by voltage-gated calcium channels. We find that nicotinic signaling, in contrast, activates CREB and gene expression in ciliary ganglion neurons both in culture and in situ only if voltage-gated channels are silent. The nicotinic response requires calcium influx and release from internal stores and acts through CaMK and MAPK pathways to sustain activated CREB. Voltage-gated channels mobilize CaMK to activate CREB initially, but they also enable calcineurin and PP1 to terminate the activation before transcription is affected. L-type voltage-gated channels dominate the outcome and block the effects of nicotinic signaling on transcription. This demonstrates a novel aspect of activity-dependent gene regulation.