Rapid synaptic remodeling by protein kinase C: Reciprocal translocation of NMDA receptors and calcium/calmodulin-dependent kinase II
Rapid synaptic remodeling by protein kinase C: Reciprocal translocation of NMDA receptors and calcium/calmodulin-dependent kinase II
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DOI：
10.1523/jneurosci.22-06-02153.2002
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发表时间：
2002-03-15
影响因子：
5.3
通讯作者：
Craig, AM
中科院分区：
文献类型：
--
作者：
Fong, DK;Rao, A;Craig, AM
与AMPA受体的快速调节相反，先前的证据支持NMDA型谷氨酸受体的突触密度是相当静态的，只在很长一段时间内以稳态的方式进行调节。本文报道用佛波酯选择性激活蛋白激酶C(PKC)，使培养的大鼠海马神经元NMDA受体从突触膜迅速扩散到突触外膜。激活PKC可诱导钙/钙调素依赖的激酶II(CaMKII)同时转位到突触，但不改变突触的脊柱数、突触前终末数、AMPA受体或突触支架蛋白PSD-95的分布。PKC诱导的CaMKII的聚集依赖于丝状肌动蛋白，而NMDA受体的扩散是通过独立于肌动蛋白或CaMKII的不同机制发生的。佛波酯处理可降低兴奋性毒性，与NMDA受体突触密度降低一致。这些结果揭示了谷氨酸能突触后特化的分子组成和功能特性的惊人的动态性质。
In contrast to the rapid regulation of AMPA receptors, previous evidence has supported the idea that the synaptic density of NMDA-type glutamate receptors is fairly static, modulated only over a long time scale in a homeostatic manner. We report here that selective activation of protein kinase C (PKC) with phorbol esters induces a rapid dispersal of NMDA receptors from synaptic to extrasynaptic plasma membrane in cultured rat hippocampal neurons. PKC activation induced a simultaneous translocation of calcium/calmodulin-dependent kinase II (CaMKII) to synapses but no change in spine number, presynaptic terminal number, or the distribution of AMPA receptors or the synaptic scaffolding protein PSD-95. PKC-induced accumulation of CaMKII was dependent on filamentous actin, whereas dispersal of NMDA receptors occurred by a different mechanism independent of actin or CaMKII. Consistent with the decrease in synaptic density of NMDA receptors, phorbol ester pretreatment reduced excitotoxicity. These results reveal a surprisingly dynamic nature to the molecular composition and functional properties of glutamatergic postsynaptic specializations.