KCC2 Gates Activity-Driven AMPA Receptor Traffic through Cofilin Phosphorylation
KCC2 Gates Activity-Driven AMPA Receptor Traffic through Cofilin Phosphorylation
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DOI：
10.1523/jneurosci.1735-15.2015
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发表时间：
2015-12-02
影响因子：
5.3
通讯作者：
Poncer, Jean Christophe
中科院分区：
文献类型：
--
作者：
Chevy, Quentin;Heubl, Martin;Poncer, Jean Christophe
神经元K/Cl转运蛋白KCC 2的表达在整个发育过程中受到正常和病理性神经元活动的严格调控。KCC 2表达的变化通常与氯稳态和GABA信号的改变有关。然而，最近的证据支持KCC 2通过仍然知之甚少的机制在突触的发育和功能中的作用。在这里，我们表明，抑制大鼠海马神经元中的KCC 2表达排除了长时程增强的AMPA受体的活动驱动的膜传递，特别是通过阻止突触。这种作用是独立的KCC 2转运蛋白功能，可以解释为增加Rac 1/PAK和LIMK依赖性的cofilin磷酸化和肌动蛋白聚合在树突棘。我们的研究结果表明，KCC 2起着至关重要的作用，在调节脊柱肌动蛋白细胞骨架和门在皮层神经元兴奋性突触的长期可塑性。
Expression of the neuronal K/Cl transporter KCC2 is tightly regulated throughout development and by both normal and pathological neuronal activity. Changes in KCC2 expression have often been associated with altered chloride homeostasis and GABA signaling. However, recent evidence supports a role of KCC2 in the development and function of glutamatergic synapses through mechanisms that remain poorly understood. Here we show that suppressing KCC2 expression in rat hippocampal neurons precludes long-term potentiation of glutamatergic synapses specifically by preventing activity-driven membrane delivery of AMPA receptors. This effect is independent of KCC2 transporter function and can be accounted for by increased Rac1/PAK- and LIMK-dependent cofilin phosphorylation and actin polymerization in dendritic spines. Our results demonstrate that KCC2 plays a critical role in the regulation of spine actin cytoskeleton and gates long-term plasticity at excitatory synapses in cortical neurons.