Activity-driven mobilization of post-synaptic proteins
Activity-driven mobilization of post-synaptic proteins
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DOI：
10.1111/j.1460-9568.2009.07007.x
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发表时间：
2009-12-01
影响因子：
3.4
通讯作者：
Colicos, Michael A.
中科院分区：
文献类型：
--
作者：
Gutierrez, R. Carolina;Flynn, Robyn;Colicos, Michael A.
在中枢神经系统发育期间建立的突触可以通过突触的消除和形成来修改。这些过程在一定程度上依赖于活动，需要对突触后成分的运输进行调控。在这里，我们研究了培养14天的大鼠海马神经元的活动驱动的重塑，重点是突触后蛋白PSD-95、Shank、神经连接蛋白(NL)1和肌动蛋白。通过实时成像和光导刺激，我们发现高频活动改变了PSD-95-GFP和Shank-YFP簇的轨迹，而不是速度，而它降低了N11簇的速度，增加了NL1簇的数量。Actin-CFP在活动后重组为小斑点，类似于50%的新小斑点与NL1簇共定位。NL1过表达促进肌动蛋白重组，而NL1突变体NL1-R473C的表达则抑制肌动蛋白重组。这些结果表明，活动依赖的变化可能导致新的突触后位置的形成，并表明NL1调节肌动蛋白重组。这些结果还表明，兴奋性突触的发育性和活性依赖性重塑都有一个共同的机制。
Synapses established during central nervous system development can be modified through synapse elimination and formation. These processes are, in part, activity dependent and require regulated trafficking of post-synaptic components. Here, we investigate the activity-driven remodeling of cultured rat hippocampal neurons at 14 days in vitro, focusing on the post-synaptic proteins PSD-95, Shank, neuroligin (NL)1 and actin. Using live imaging and photoconductive stimulation, we found that high-frequency activity altered the trajectory, but not velocity, of PSD-95-GFP and Shank-YFP clusters, whereas it reduced the speed and increased the number of NL1 clusters. Actin-CFP reorganized into puncta following activity and similar to 50% of new puncta colocalized with NL1 clusters. Actin reorganization was enhanced by the overexpression of NL1 and decreased by the expression of an NL1 mutant, NL1-R473C. These results demonstrate activity-dependent changes that may result in the formation of new post-synaptic sites and suggest that NL1 modulates actin reorganization. The results also suggest that a common mechanism underlies both the developmental and activity-dependent remodeling of excitatory synapses.