Tao X, Finkbeiner S, Arnold D B, Shaywitz A J, Greenberg M E
Children's Hospital, Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Neuron. 1998 Apr;20(4):709-26. doi: 10.1016/s0896-6273(00)81010-7.
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.
CREB是一种参与调控适应性神经元反应的转录因子。尽管人们认为CREB在神经元中的一个功能是调控其产物控制突触功能的基因，但尚未确定介导突触功能的CREB靶点。本报告描述了实验，证明CREB或一种密切相关的蛋白质介导了脑源性神经营养因子（BDNF，一种调节突触活动的神经营养因子）的钙依赖性调控。在皮质神经元中，钙离子内流触发CREB的磷酸化，CREB通过与BDNF基因内的关键钙反应元件（CRE）结合来激活BDNF转录。BDNF CRE或相邻的新型调控元件的突变以及CREB功能的阻断导致BDNF转录显著丧失。这些发现表明，CREB家族成员与其他转录因子协同作用来调控BDNF转录。我们得出结论，BDNF基因是CREB家族的一个靶点，其蛋白质产物在突触处发挥作用以控制适应性神经元反应。
