Calcium regulation of neuronal gene expression
Calcium regulation of neuronal gene expression
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DOI：
10.1073/pnas.191352298
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发表时间：
2001-09-25
影响因子：
11.1
通讯作者：
Greenberg, ME
中科院分区：
文献类型：
--
作者：
West, AE;Chen, WG;Greenberg, ME
可塑性是大脑的一个显著特征，允许神经元结构和功能适应电活动的模式。这些长期变化的一个组成部分是活动驱动的新基因表达的诱导，这是与学习和记忆相关的突触传递的长期增强作用以及有助于在发育期间塑造和连接大脑的活动依赖性生存事件所必需的。我们的特点是神经元膜去极化和随后的钙离子流入细胞质导致新基因转录的诱导的分子机制。我们已经确定了这一系列事件中的三个点，在这些点上，不同类型的刺激诱导的基因的特异性可以被调节。通过使用编码脑源性神经营养因子（BDNF）的基因的诱导作为模型，我们发现钙流入诱导该基因转录的能力受钙进入细胞的途径、转录因子cAMP-反应元件（CRE）结合蛋白（CREB）上诱导的磷酸化模式、以及通过补充到BDNF启动子的活性转录因子。这些结果完善和扩展了大脑中活性诱导基因诱导的工作模型，并有助于解释不同类型的神经元刺激如何激活不同的转录反应。
Plasticity is a remarkable feature of the brain, allowing neuronal structure and function to accommodate to patterns of electrical activity. One component of these long-term changes is the activity-driven induction of new gene expression, which is required for both the long-lasting long-term potentiation of synaptic transmission associated with learning and memory, and the activity-dependent survival events that help to shape and wire the brain during development. We have characterized molecular mechanisms by which neuronal membrane depolarization and subsequent calcium influx into the cytoplasm lead to the induction of new gene transcription. We have identified three points within this cascade of events where the specificity of genes induced by different types of stimuli can be regulated. By using the induction of the gene that encodes brain-derived neurotrophic factor (BDNF) as a model, we have found that the ability of a calcium influx to induce transcription of this gene is regulated by the route of calcium entry into the cell, by the pattern of phosphorylation induced on the transcription factor cAMP-response element (CRE) binding protein (CREB), and by the complement of active transcription factors recruited to the BDNF promoter. These results refine and expand the working model of activity-induced gene induction in the brain, and help to explain how different types of neuronal stimuli can activate distinct transcriptional responses.