Neurturin evokes MAPK-dependent upregulation of Egr4 and KCC2 in developing neurons.

Neurturin evokes MAPK-dependent upregulation of Egr4 and KCC2 in developing neurons.
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DOI:
10.1155/2011/641248
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发表时间:
2011
期刊:
影响因子:
3.1
通讯作者:
Rivera C
Rivera C
中科院分区:
医学4区
文献类型:
--
作者:
Ludwig A;Uvarov P;Pellegrino C;Thomas-Crusells J;Schuchmann S;Saarma M;Airaksinen MS;Rivera C

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K-Cl协同转运蛋白KCC 2在GABA介导的反应的功能发育中起着至关重要的作用,使GABA在成年神经元中超极化。我们先前已经表明,BDNF上调KCC 2在未成熟的神经元通过转录因子Egr 4。BDNF对Egr 4和KCC 2的作用依赖于ERK 1/2的激活。在这里,我们证明,营养因子neurturin也可以触发Egr 4的表达和上调KCC 2的ERK 1/2依赖的方式。这些结果表明,Egr 4是营养因子介导的KCC 2在未成熟神经元中上调的机制中的重要组成部分,涉及BDNF和Neurturin共同的特定细胞内途径的激活。
The K-Cl cotransporter KCC2 plays a crucial role in the functional development of GABAA-mediated responses rendering GABA hyperpolarizing in adult neurons. We have previously shown that BDNF upregulates KCC2 in immature neurons through the transcription factor Egr4. The effect of BDNF on Egr4 and KCC2 was shown to be dependent on the activation of ERK1/2. Here we demonstrate that the trophic factor neurturin can also trigger Egr4 expression and upregulate KCC2 in an ERK1/2-dependent manner. These results show that Egr4 is an important component in the mechanism for trophic factor-mediated upregulation of KCC2 in immature neurons involving the activation of specific intracellular pathways common to BDNF and Neurturin.
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