Activity-dependent spine morphogenesis: a role for the actin-capping protein Eps8.
Activity-dependent spine morphogenesis: a role for the actin-capping protein Eps8.
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DOI：
10.1523/jneurosci.0998-12.2013
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发表时间：
2013-02-06
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影响因子：
--
通讯作者：
Salinas PC
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文献类型：
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作者：
Stamatakou E;Marzo A;Gibb A;Salinas PC
神经元活动通过肌动蛋白细胞骨架的变化调节树突棘的形成和形态。然而，调控这一过程的分子机制仍然知之甚少。在这里，我们报告说，Eps8，肌动蛋白帽蛋白，所需的脊柱形态发生。在大鼠海马神经元的获得和功能丧失的研究表明，Eps8促进树突棘的形成，而抑制丝状伪足的形成。Eps8的功能丧失增加肌动蛋白聚合，并诱导树突棘内的快速肌动蛋白周转，如通过游离倒刺末端和FRAP测定所揭示的，与Eps8作为肌动蛋白加帽蛋白的作用一致。有趣的是，Eps8调节棘和树突轴上兴奋性突触之间的平衡，而不影响突触总数或基础突触传递。重要的是，Eps8功能的丧失损害了由长时程增强诱导的突触的结构和功能可塑性。这些发现表明Eps8在棘形成和活性介导的突触可塑性中的新作用。
Neuronal activity regulates the formation and morphology of dendritic spines through changes in the actin cytoskeleton. However, the molecular mechanisms that regulate this process remain poorly understood. Here we report that Eps8, an actin-capping protein, is required for spine morphogenesis. In rat hippocampal neurons gain and loss of function studies demonstrate that Eps8 promotes the formation of dendritic spines, whereas inhibits filopodium formation. Loss of function of Eps8 increases actin polymerization and induces fast actin turnover within dendritic spines, as revealed by free barbed-end and FRAP assays, consistent with a role for Eps8 as an actin-capping protein. Interestingly, Eps8 regulates the balance between excitatory synapses on spines and on the dendritic shaft, without affecting the total number of synapses or basal synaptic transmission. Importantly, Eps8 loss of function impairs the structural and functional plasticity of synapses induced by long-term potentiation. These findings demonstrate a novel role for Eps8 in spine formation and in activity-mediated synaptic plasticity.