PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity
PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity
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DOI：
10.1038/nn997
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发表时间：
2003-02-01
影响因子：
25
通讯作者：
Malinow, R
中科院分区：
文献类型：
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作者：
Esteban, JA;Shi, SH;Malinow, R
AMPA 受体在突触中的调节整合对于突触可塑性非常重要。在这里，我们研究了蛋白激酶 A (PKA) 在此过程中的作用。我们发现，AMPA 受体亚基 GluR4 和 GluR1 的 PKA 磷酸化直接控制大鼠海马器官切片中 AMPA 受体的突触掺入。 GluR4 的活性驱动 PKA 磷酸化对于缓解保留相互作用并驱动受体进入突触是必要且充分的。相反，GluR1 的 PKA 磷酸化和钙/钙调蛋白依赖性激酶 II (CaMKII) 的活性都是受体掺入所必需的。因此，AMPA 受体亚基的 PKA 磷酸化有助于突触可塑性的多种机制。
The regulated incorporation of AMPA receptors into synapses is important for synaptic plasticity. Here we examine the role of protein kinase A (PKA) in this process. We found that PKA phosphorylation of the AMPA receptor subunits GluR4 and GluR1 directly controlled the synaptic incorporation of AMPA receptors in organotypic slices from rat hippocampus. Activity-driven PKA phosphorylation of GluR4 was necessary and sufficient to relieve a retention interaction and drive receptors into synapses. In contrast, PKA phosphorylation of GluR1 and the activity of calcium/calmodulin-dependent kinase II (CaMKII) were both necessary for receptor incorporation. Thus, PKA phosphorylation of AMPA receptor subunits contributes to diverse mechanisms underlying synaptic plasticity.