Binding of the inward rectifier K+ channel Kir 2.3 to PSD-95 is regulated by protein kinase A phosphorylation
Binding of the inward rectifier K+ channel Kir 2.3 to PSD-95 is regulated by protein kinase A phosphorylation
复制标题
DOI：
10.1016/s0896-6273(00)80207-x
复制
发表时间：
1996-10-01
期刊：
影响因子：
16.2
通讯作者：
Bredt, DS
中科院分区：
文献类型：
--
作者：
Cohen, NA;Brenman, JE;Bredt, DS
离子通道与细胞骨架相互作用的动态调节介导突触可塑性的各个方面，但这一过程的机制在很大程度上是未知的。在这里，我们报告说，两个内向整流K+通道，Kir 2.1和2.3，结合PSD-95，一种细胞骨架蛋白的突触后密度，集群NMDA受体和电压依赖性K+通道。Kir 2.3与PSD-95共定位于前脑的神经元群体中，并且PSD-95/Kir 2.3复合物出现在海马中。在Kir 2.3的C-末端尾部内，一个与PSD-95相互作用的关键丝氨酸残基也是蛋白激酶A（PKA）磷酸化的底物。完整细胞中PKA的刺激导致通道从PSD-95快速解离。这项工作确定了一个生理机制，调节离子通道与突触后密度的相互作用。
Dynamic regulation of ion channel interactions with the cytoskeleton mediates aspects of synaptic plasticity, yet mechanisms for this process are largely unknown. Here, we report that two inwardly rectifying K+ channels, Kir 2.1 and 2.3, bind to PSD-95, a cytoskeletal protein of postsynaptic densities that clusters NMDA receptors and voltage-dependent K+ channels. Kir 2.3 colocalizes with PSD-95 in neuronal populations in forebrain, and a PSD-95/Kir 2.3 complex occurs in hippocampus. Within the C-terminal tail of Kir 2.3, a serine residue critical for interaction with PSD-95, is also a substrate for phosphorylation by protein kinase A (PKA). Stimulation of PKA in intact cells causes rapid dissociation of the channel from PSD-95. This work identifies a physiological mechanism for regulating ion channel interactions with the postsynaptic density.