Early Growth Response 4 Mediates BDNF Induction of Potassium Chloride Cotransporter 2 Transcription
Early Growth Response 4 Mediates BDNF Induction of Potassium Chloride Cotransporter 2 Transcription
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DOI：
10.1523/jneurosci.2006-10.2011
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发表时间：
2011-01-12
影响因子：
5.3
通讯作者：
Rivera, Claudio
中科院分区：
文献类型：
--
作者：
Ludwig, Anastasia;Uvarov, Pavel;Rivera, Claudio
中枢神经系统GABA能传递成熟的一个重要事件是GABA(A)介导的反应从去极化到超极化的质变。在皮质区域，这归因于KCC2b(KCC2b)的表达增加，KCC2b是神经元特异性K-Cl协转运体KCC2的主要亚型。我们先前已经证明转录因子早期生长反应4(Egr4)可以激活KCC2b启动子。在这里，我们证明了在未成熟的海马神经元中，BDNF强烈地诱导ERK1/2(细胞外信号调节激酶1/2)依赖的Egr4表达和KCC2b启动子依赖于Egr4的快速激活。随后KCC2b mRNA的增加有助于KCC2总蛋白水平的表达。这些结果表明，在未成熟神经元中，Egr4是BDNF依赖的KCC2基因通过ERK1/2途径进行调控的重要组成部分。
A major event in the maturation of CNS GABAergic transmission is the qualitative change in GABA(A)-mediated responses from depolarizing to hyperpolarizing. In cortical regions, this is attributed to the increased expression of potassium chloride cotransporter 2b (KCC2b), the main isoform of the neuron-specific K-Cl cotransporter KCC2. We have previously shown that transcription factor early growth response 4 (Egr4) can activate the KCC2b promoter. Here we demonstrate that in immature hippocampal neurons BDNF robustly induces ERK1/2 (extracellular signal-regulated kinase 1/2)-dependent Egr4 expression and rapid Egr4-dependent activation of the KCC2b promoter. The subsequent increase in KCC2b mRNA contributes to the expression of total KCC2 protein levels. These results indicate that Egr4 is an important component in the mechanism of BDNF-dependent KCC2 gene regulation via the ERK1/2 pathway in immature neurons.