Neuronal activity-dependent cell survival mediated by transcription factor MEF2
Neuronal activity-dependent cell survival mediated by transcription factor MEF2
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DOI：
10.1126/science.286.5440.785
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发表时间：
1999-10-22
期刊：
影响因子：
56.9
通讯作者：
Greenberg, ME
中科院分区：
文献类型：
--
作者：
Mao, ZX;Bonni, A;Greenberg, ME
在哺乳动物发育过程中，电活动促进已建立适当突触连接的神经元的钙依赖性存活。然而，钙介导发育过程中神经元存活的机制尚不清楚。确定了一种转录依赖性机制，钙流入神经元可促进细胞存活。转录因子 MEF2 在新生成的有丝分裂后神经元中选择性表达，并且是这些神经元生存所必需的。钙流入小脑颗粒神经元导致 p38 丝裂原激活蛋白激酶依赖性磷酸化的激活和 MEF2 的激活。一旦激活，MEF2 通过刺激 MEF2 依赖性基因转录来调节神经元存活。这些发现表明MEF2是一种钙调节转录因子，并定义了MEF2在神经系统发育过程中的功能，该功能不同于之前明确描述的MEF2在肌肉分化过程中的功能。
During mammalian development, electrical activity promotes the calcium-dependent survival of neurons that have made appropriate synaptic connections. However, the mechanisms by which calcium mediates neuronal survival during development are not well characterized. A transcription-dependent mechanism was identified by which calcium influx into neurons promoted cell survival. The transcription factor MEF2 was selectively expressed in newly generated postmitotic neurons and was required for the survival of these neurons. Calcium influx into cerebellar granule neurons Led to activation of p38 mitogen-activated protein kinase-dependent phosphorylation and activation of MEF2. Once activated, MEF2 regulated neuronal survival by stimulating MEF2-dependent gene transcription. These findings demonstrate that MEF2 is a calcium-regulated transcription factor and define a function for MEF2 during nervous system development that is distinct from previously Well-characterized functions of MEF2 during muscle differentiation.