Rapid turnover of actin in dendritic spines and its regulation by activity
Rapid turnover of actin in dendritic spines and its regulation by activity
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DOI：
10.1038/nn811
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发表时间：
2002-03-01
影响因子：
25
通讯作者：
Murthy, VN
中科院分区：
文献类型：
--
作者：
Star, EN;Kwiatkowski, DJ;Murthy, VN
树突棘是含有高浓度丝状肌动蛋白的活动结构。利用表达荧光肌动蛋白的海马神经元和光漂白后荧光恢复的方法，我们发现脊柱中有85+/-2%的肌动蛋白是动态的，其转换时间为44.2+/-4.0 s。这种快速的转换与当前的模型不兼容，该模型调用大量稳定的纤维和纤维与突触后组分的静态耦合。已知在这些神经元中引起长期抑制的低频刺激稳定了脊柱中近一半的动态肌动蛋白。这种作用取决于n -甲基- d -天冬氨酸（NMDA）受体的激活和钙的流入。在缺乏凝胶蛋白（一种钙依赖的肌动蛋白结合蛋白）的小鼠神经元中，肌动蛋白的活性依赖稳定性受损。我们的研究为脊髓中肌动蛋白转换的动力学、神经活动对其的调节及其机制提供了新的信息。
Dendritic spines are motile structures that contain high concentrations of filamentous actin. Using hippocampal neurons expressing fluorescent actin and the method of fluorescence recovery after photobleaching, we found that 85+/-2% of actin in the spine was dynamic, with a turnover time of 44.2+/-4.0 s. The rapid turnover is not compatible with current models invoking a large population of stable filaments and static coupling of filaments to postsynaptic components. Low-frequency stimulation known to induce long-term depression in these neurons stabilized nearly half the dynamic actin in the spine. This effect depended on the activation of N-methyl-D-aspartate (NMDA) receptors and the influx of calcium. In neurons from mice lacking gelsolin, a calcium-dependent actin-binding protein, activity-dependent stabilization of actin was impaired. Our studies provide new information on the kinetics of actin turnover in spines, its regulation by neural activity and the mechanisms involved in this regulation.