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首页> 外文期刊>Journal of Neurophysiology >Multiple components of eIF4F are required for protein synthesis-dependent hippocampal long-term potentiation
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Multiple components of eIF4F are required for protein synthesis-dependent hippocampal long-term potentiation

机译：eIF4F的多个组件是依赖蛋白合成的海马长时程增强所必需的

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Persistent forms of synaptic plasticity are widely thought to require the synthesis of new proteins. This feature of long-lasting forms of plasticity largely has been demonstrated using inhibitors of general protein synthesis, such as either anisomycin or emetine. However, these drugs, which inhibit elongation, cannot address detailed questions about the regulation of translation initiation, where the majority of translational control occurs. Moreover, general protein synthesis inhibitors cannot distinguish between cap-dependent and cap-independent modes of translation initiation. In the present study, we took advantage of two novel compounds, 4EGI-1 and hippuristanol, each of which targets a different component of the eukaryotic initiation factor (eIF)4F initiation complex, and investigated their effects on long-term potentiation (LTP) at CA3-CA1 synapses in the hippocampus. We found that 4EGI-1 and hippuristanol both attenuated long-lasting late-phase LTP induced by two different stimulation paradigms. We also found that 4EGI-1 and hippuristanol each were capable of blocking the expression of newly synthesized proteins immediately after the induction of late-phase LTP. These new pharmacological tools allow for a more precise dissection of the role played by translational control pathways in synaptic plasticity and demonstrate the importance of multiple aspects of eIF4F in processes underlying hippocampal LTP, laying the foundation for future studies investigating the role of eIF4F in hippocampus-dependent memory processes. ? 2013 the American Physiological Society.
机译：持久形式的突触可塑性被广泛认为需要合成新蛋白质。使用一般的蛋白质合成抑制剂（如茴香霉素或依替丁）已证明了这种持久形式的可塑性。但是，这些抑制伸长的药物无法解决有关翻译起始调控的详细问题，因为大多数翻译控制发生在翻译起始调控上。而且，一般的蛋白质合成抑制剂不能区分翻译起始的帽依赖性和帽依赖性模式。在本研究中，我们利用了两种新型化合物4EGI-1和hippuristanol，它们各自靶向真核生物起始因子（eIF）4F起始复合物的不同成分，并研究了它们对长期增强（LTP）的影响在海马CA3-CA1突触。我们发现，4EGI-1和马尿固醇均减弱了由两种不同刺激范式诱导的长期晚期LTP。我们还发现，在诱导晚期LTP后，4EGI-1和马嘌呤醇均能够立即阻断新合成蛋白质的表达。这些新的药理学工具可以更精确地剖析翻译控制途径在突触可塑性中的作用，并证明eIF4F在海马LTP潜在过程中的多个方面的重要性，为进一步研究eIF4F在海马体中的作用奠定了基础。依赖的存储过程。 ？ 2013年美国生理学会。

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