Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number
Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number
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DOI：
10.1126/science.1122511
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发表时间：
2006-02-17
期刊：
影响因子：
56.9
通讯作者：
Greenberg, ME
中科院分区：
文献类型：
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作者：
Flavell, SW;Cowan, CW;Greenberg, ME
在哺乳动物的神经系统中，神经元活动调节突触形成的强度和数量。人们对协调这一过程的遗传程序知之甚少。我们发现，当海马神经元形成突触时，肌细胞增强因子2 （MEF2）转录因子以神经元活性和钙调磷酸酶依赖的方式抑制兴奋性突触数量。作为对神经元活性增加的反应，钙流入神经元诱导钙/钙调素调节的磷酸酶钙调磷酸酶的激活，该酶去磷酸化并激活MEF2。当MEF2被激活时，它可以促进一系列限制突触数量的基因的转录，包括arc和synGAP。这些发现定义了一个活动依赖的转录程序，可能在发育过程中控制突触数量。
In the mammalian nervous system, neuronal activity regulates the strength and number of synapses formed. The genetic program that coordinates this process is poorly understood. We show that myocyte enhancer factor 2 (MEF2) transcription factors suppressed excitatory synapse number in a neuronal activity- and calcineurin-dependent manner as hippocampal neurons formed synapses. In response to increased neuronal activity, calcium influx into neurons induced the activation of the calcium/calmodulin-regulated phosphatase calcineurin, which dephosphorylated and activated MEF2. When activated, MEF2 promoted the transcription of a set of genes, including arc and synGAP, that restrict synapse number. These findings define an activity-dependent transcriptional program that may control synapse number during development.