Fong Dan K, Rao Anuradha, Crump F Thomas, Craig Ann Marie
Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Neurosci. 2002 Mar 15;22(6):2153-64. doi: 10.1523/JNEUROSCI.22-06-02153.2002.
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.
与AMPA受体的快速调节相反，先前的证据支持这样一种观点，即NMDA型谷氨酸受体的突触密度相当稳定，仅在长时间尺度上以稳态方式进行调节。我们在此报告，用佛波酯选择性激活蛋白激酶C（PKC）会诱导培养的大鼠海马神经元中NMDA受体从突触向突触外质膜快速分散。PKC激活诱导钙/钙调蛋白依赖性激酶II（CaMKII）同时向突触转运，但棘突数量、突触前终末数量、AMPA受体分布或突触支架蛋白PSD-95均无变化。PKC诱导的CaMKII积累依赖于丝状肌动蛋白，而NMDA受体的分散则通过一种独立于肌动蛋白或CaMKII的不同机制发生。与NMDA受体突触密度的降低一致，佛波酯预处理降低了兴奋性毒性。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具有惊人的动态性质。
