Staufen1 regulation of protein synthesis-dependent long-term potentiation and synaptic function in hippocampal pyramidal cells
Staufen1 regulation of protein synthesis-dependent long-term potentiation and synaptic function in hippocampal pyramidal cells
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DOI：
10.1128/mcb.01844-07
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发表时间：
2008-05-01
影响因子：
5.3
通讯作者：
Lacaille, Jean-Claude
中科院分区：
文献类型：
--
作者：
Lebeau, Genevieve;Maher-Laporte, Marjolaine;Lacaille, Jean-Claude
Staufen1 (Stau1) 是一种 RNA 结合蛋白，参与 mRNA 的运输、定位、衰变和翻译控制。在神经元中，它存在于细胞体中，也存在于沿着树突运输的 RNA 颗粒中。树突 mRNA 定位可能与长期突触可塑性和记忆有关。为了确定 Stau1 在突触功能中的作用，我们使用小干扰 RNA (siRNA) 检查了海马切片培养物中 Stau1 下调的影响。 Stau1 siRNA 的基因枪转染导致切片培养物中 Stau1 的选择性下调。与 Stau1 在运输突触可塑性所需 mRNA 中的作用一致，Stau1 下调会损害晚期形式的化学诱导的长期增强 (L-LTP)，而不影响早期 LTP、mGluR1/5 介导的长期抑制或基础诱发的突触传递。 Stau1 下调降低了微型兴奋性突触后电流的幅度和频率，表明其在维持海马突触功效中发挥着作用。在细胞水平上，Stau1 下调将脊柱形状从规则的脊柱转变为拉长的脊柱，而脊柱密度没有变化。脊柱形状的变化可以通过抗RNA干扰的Stau1亚型来挽救。因此，Stau1 对于树突 mRNA 的加工和/或运输非常重要，而树突 mRNA 对于调节突触强度和维持海马依赖性学习和记忆的功能连接变化至关重要。
Staufen1 (Stau1) is an RNA-binding protein involved in transport, localization, decay, and translational control of mRNA. In neurons, it is present in cell bodies and also in RNA granules which are transported along dendrites. Dendritic mRNA localization might be involved in long-term synaptic plasticity and memory. To determine the role of Stau1 in synaptic function, we examined the effects of Stau1 down-regulation in hippocampal slice cultures using small interfering RNA (siRNA). Biolistic transfection of Stau1 siRNA resulted in selective down-regulation of Stau1 in slice cultures. Consistent with a role of Stau1 in transporting mRNAs required for synaptic plasticity, Stau1 down-regulation impaired the late form of chemically induced long-term potentiation (L-LTP) without affecting early-LTP, mGluR1/5-mediated long-term depression, or basal evoked synaptic transmission. Stau1 down-regulation decreased the amplitude and frequency of miniature excitatory postsynaptic currents, suggesting a role in maintaining efficacy at hippocampal synapses. At the cellular level, Stau1 down-regulation shifted spine shape from regular to elongated spines, without changes in spine density. The change in spine shape could be rescued by an RNA interference-resistant Stau1 isoform. Therefore, Stau1 is important for processing and/or transporting in dendrites mRNAs that are critical in regulation of synaptic strength and maintenance of functional connectivity changes underlying hippocampus-dependent learning and memory.