Protein kinase a mediates activity-dependent Kv4.2 channel trafficking.
Protein kinase a mediates activity-dependent Kv4.2 channel trafficking.
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DOI：
10.1523/jneurosci.1951-08.2008
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发表时间：
2008-07-23
期刊：
影响因子：
--
通讯作者：
Hoffman DA
中科院分区：
文献类型：
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作者：
Hammond RS;Lin L;Sidorov MS;Wikenheiser AM;Hoffman DA
A型钾通道亚基Kv4.2通过调节树突兴奋性影响海马功能，Kv4.2表面表达的变化改变突触可塑性。我们实验室的最新数据表明，EGFP（增强型绿色荧光蛋白）标记的Kv4.2通道位于树突棘内的活动依赖性的方式后，突触刺激和化学诱导的长时程增强。然而，Kv4.2内化的分子触发因素仍然未知。在这里，我们研究了蛋白激酶A（PKA）在Kv4.2活性依赖性运输中的作用。在海马神经元中，PKA激活与forskolin或8-Br-cAMP诱导Kv4.2从树突棘的内化，而PKA抑制与H89阻止AMPA诱导的内化。此外，在Kv4.2的C-末端PKA磷酸化位点（S552 A）处引入点突变阻止了AMPA诱导的Kv4.2内化。总之，这些数据表明Kv4.2活性依赖性内化需要Kv4.2在丝氨酸522处的PKA磷酸化。
The A-type potassium channel subunit Kv4.2 influences hippocampal function through regulation of dendritic excitability, and changes in Kv4.2 surface expression alter synaptic plasticity. Recent data from our laboratory demonstrate that EGFP (enhanced green fluorescent protein)-tagged Kv4.2 channels located in dendritic spines are internalized in an activity-dependent manner after synaptic stimulation and during chemically induced long-term potentiation. However, the molecular trigger for Kv4.2 internalization remains unknown. Here we examined the role of protein kinase A (PKA) in Kv4.2 activity-dependent trafficking. In hippocampal neurons, PKA activation with forskolin or 8-Br-cAMP induced Kv4.2 internalization from dendritic spines, whereas PKA inhibition with H89 prevented AMPA-induced internalization. Furthermore, introduction of a point mutation at the C-terminal PKA phosphorylation site of Kv4.2 (S552A) prevented the AMPA-induced internalization of Kv4.2. Together, these data demonstrate that Kv4.2 activity-dependent internalization requires PKA phosphorylation of Kv4.2 at serine 522.