Sutton Michael A, Taylor Anne M, Ito Hiroshi T, Pham Anh, Schuman Erin M
Division of Biology 114-96, California Institute of Technology, Pasadena, CA 91125, USA.
Neuron. 2007 Aug 16;55(4):648-61. doi: 10.1016/j.neuron.2007.07.030.
Activity-dependent regulation of dendritic protein synthesis is critical for enduring changes in synaptic function, but how the unique features of distinct activity patterns are decoded by the dendritic translation machinery remains poorly understood. Here, we identify eukaryotic elongation factor-2 (eEF2), which catalyzes ribosomal translocation during protein synthesis, as a biochemical sensor in dendrites that is specifically and locally tuned to the quality of neurotransmission. We show that intrinsic action potential (AP)-mediated network activity in cultured hippocampal neurons maintains eEF2 in a relatively dephosphorylated (active) state, whereas spontaneous neurotransmitter release (i.e., miniature neurotransmission) strongly promotes the phosphorylation (and inactivation) of eEF2. The regulation of eEF2 phosphorylation is responsive to bidirectional changes in miniature neurotransmission and is controlled locally in dendrites. Finally, direct spatially controlled inhibition of eEF2 phosphorylation induces local translational activation, suggesting that eEF2 is a biochemical sensor that couples miniature synaptic events to local translational suppression in neuronal dendrites.
依赖活动的树突蛋白合成调节对于突触功能的持久变化至关重要，但树突翻译机制如何解码不同活动模式的独特特征仍知之甚少。在这里，我们确定真核延伸因子2（eEF2），其在蛋白质合成过程中催化核糖体易位，是树突中的一种生化传感器，它被特异性地且局部地调节以适应神经传递的质量。我们表明，培养的海马神经元中内在动作电位（AP）介导的网络活动使eEF2维持在相对去磷酸化（活跃）状态，而自发神经递质释放（即微小神经传递）强烈促进eEF2的磷酸化（和失活）。eEF2磷酸化的调节对微小神经传递的双向变化有反应，并在树突中局部受到控制。最后，对eEF2磷酸化的直接空间控制抑制诱导局部翻译激活，表明eEF2是一种生化传感器，它将微小突触事件与神经元树突中的局部翻译抑制联系起来。
