Protein Kinase C Promotes N-Methyl-D-aspartate (NMDA) Receptor Trafficking by Indirectly Triggering Calcium/Calmodulin-dependent Protein Kinase II (CaMKII) Autophosphorylation
Protein Kinase C Promotes N-Methyl-D-aspartate (NMDA) Receptor Trafficking by Indirectly Triggering Calcium/Calmodulin-dependent Protein Kinase II (CaMKII) Autophosphorylation
复制标题
蛋白激酶 C 通过间接触发钙/钙调蛋白依赖性蛋白激酶 II (CaMKII) 自磷酸化来促进 N-甲基-D-天冬氨酸 (NMDA) 受体运输
DOI：
10.1074/jbc.m110.192708
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发表时间：
2011-07-15
影响因子：
4.8
通讯作者：
Lu, Wei
中科院分区：
文献类型：
--
作者：
Yan, Jing-Zhi;Xu, Zhuo;Lu, Wei
神经元NMDA受体（NMDAR）的调节在突触传递和可塑性中至关重要。蛋白激酶C（PKC）通过与NMDAR相关蛋白（NAP）相互作用促进NMDAR运输至细胞表面。然而，关于对PKC诱导的NMDAR贩运至关重要的NAP知之甚少。在这里，我们表明，钙/钙调蛋白依赖性蛋白激酶II（CaMKII）可能是一个NAP，介导的增强NMDAR贩运的PKC。PKC激活促进了自磷酸化CaMKII的水平，并增加了与NMDAR的关联，伴随着功能性NMDAR插入，在突触后位点。这种增强作用，沿着PKC诱导的AMPA受体介导的反应的长时程增强作用，被CaMK Ⅱ拮抗剂或通过干扰CaMK Ⅱ和NR 2A或NR 2B之间的相互作用消除。进一步的相互阻断实验表明，PKC和CaMK II在NMDAR运输和长时程增强（LTP）诱导的增强中共享共同的信号通路。我们的研究结果表明，PKC促进NMDA受体的运输，并通过间接触发CaMK II自磷酸化和随后增加与NMDAR的关联诱导突触可塑性。
Regulation of neuronal NMDA receptor (NMDAR) is critical in synaptic transmission and plasticity. Protein kinase C (PKC) promotes NMDAR trafficking to the cell surface via interaction with NMDAR-associated proteins (NAPs). Little is known, however, about the NAPs that are critical to PKC-induced NMDAR trafficking. Here, we showed that calcium/calmodulin-dependent protein kinase II (CaMKII) could be a NAP that mediates the potentiation of NMDAR trafficking by PKC. PKC activation promoted the level of autophosphorylated CaMKII and increased association with NMDARs, accompanied by functional NMDAR insertion, at postsynaptic sites. This potentiation, along with PKC-induced long term potentiation of the AMPA receptor-mediated response, was abolished by CaMKII antagonist or by disturbing the interaction between CaMKII and NR2A or NR2B. Further mutual occlusion experiments demonstrated that PKC and CaMKII share a common signaling pathway in the potentiation of NMDAR trafficking and long-term potentiation (LTP) induction. Our results revealed that PKC promotes NMDA receptor trafficking and induces synaptic plasticity through indirectly triggering CaMKII autophosphorylation and subsequent increased association with NMDARs.