Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism
Ca2+ influx regulates BDNF transcription by a CREB family transcription factor-dependent mechanism
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DOI：
10.1016/s0896-6273(00)81010-7
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发表时间：
1998-04-01
期刊：
影响因子：
16.2
通讯作者：
Greenberg, ME
中科院分区：
文献类型：
--
作者：
Tao, X;Finkbeiner, S;Greenberg, ME
CREB是一种参与控制适应性神经元反应的转录因子。虽然CREB在神经元中的功能之一被认为是调节其产物控制突触功能的基因，但尚未确定CREB介导突触功能的靶点。本报告描述了实验证明CREB或密切相关的蛋白质介导的BDNF，神经营养因子，调节突触活动的Ca 2+依赖性调节。在皮质神经元中，Ca2+内流触发CREB的磷酸化，CREB通过与BDNF基因内的关键Ca2+反应元件（CRE）结合来激活BDNF转录。BDNF CRE或邻近的新调控元件的突变以及CREB功能的阻断导致BDNF转录的急剧丧失。这些发现表明CREB家族成员与另外的转录因子合作调节BDNF转录。我们的结论是，BDNF基因是CREB家族的目标，其蛋白质产物的功能在突触控制适应性神经元反应。
CREB is a transcription factor implicated in the control of adaptive neuronal responses. Although one function of CREB in neurons is believed to be the regulation of genes whose products control synaptic function, the targets of CREB that mediate synaptic function have not yet been identified. This report describes experiments demonstrating that CREB or a closely related protein mediates Ca2+-dependent regulation of BDNF, a neurotrophin that modulates synaptic activity. In cortical neurons, Ca2+ influx triggers phosphorylation of CREB, which by binding to a critical Ca2+ response element (CRE) within the BDNF gene activates BDNF transcription. Mutation of the BDNF CRE or an adjacent novel regulatory element as well as a blockade of CREB function resulted in a dramatic loss of BDNF transcription. These findings suggest that a CREB family member acts cooperatively with an additional transcription factor(s) to regulate BDNF transcription. We conclude that the BDNF gene is a CREB family target whose protein product functions at synapses to control adaptive neuronal responses.