ADF/cofilin-mediated actin dynamics regulate AMPA receptor trafficking during synaptic plasticity.

ADF/cofilin-mediated actin dynamics regulate AMPA receptor trafficking during synaptic plasticity.
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DOI:
10.1038/nn.2634
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发表时间:
2010-10
影响因子:
25
通讯作者:
Zheng, James Q.
Zheng, James Q.
中科院分区:
医学1区
文献类型:
--
作者:
Gu, Jiaping;Lee, Chi Wai;Fan, Yanjie;Komlos, Daniel;Tang, Xin;Sun, Chicheng;Yu, Kuai;Hartzell, H. Criss;Chen, Gong;Bamburg, James R.;Zheng, James Q.

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树突棘在突触可塑性过程中经历基于肌动蛋白的生长和收缩。肌动蛋白解聚因子(ADF)/cofilin家族肌动蛋白相关蛋白在脊柱可塑性中起重要作用。升高的ADF/cofilin活性通常导致脊柱尺寸减小和脊柱形态不成熟,但在某些情况下可以增强突触增强。因此,ADF/cofilin可能对突触后结构和功能有不同的影响。在这里,我们报告说,ADF/cofilin介导的肌动蛋白动态调节AMPA受体(AMPAR)的贩运过程中的突触增强,这是不同的肌动蛋白的结构作用,在脊柱形态。我们发现,ADF/cofilin活性的升高显着增强化学诱导的LTP(cLTP)后的AMPAR的表面添加,而ADF/cofilin的抑制废除AMPAR添加。我们的数据进一步表明,cLTP eliminate的ADF/cofilin去磷酸化和磷酸化的时间序列的基础AMPAR运输和脊柱扩大。这些研究结果表明,在突触可塑性的受体数量和脊柱大小的突触后修饰的时间调节ADF/cofilin活动的一个新的作用。
Dendritic spines undergo actin-based growth and shrinkage during synaptic plasticity. The actin depolymerizing factor (ADF)/cofilin family of actin-associated proteins plays important roles in spine plasticity. Elevated ADF/cofilin activities often lead to reduced spine size and immature spine morphology, but can enhance synaptic potentiation in some cases. Therefore ADF/cofilin may exert distinct effects on postsynaptic structure and function. Here we report that ADF/cofilin-mediated actin dynamics regulate AMPA receptor (AMPAR) trafficking during synaptic potentiation, which is distinct from actin's structural role in spine morphology. We find that elevated ADF/cofilin activity markedly enhances surface addition of AMPARs after chemically-induced LTP (cLTP), whereas inhibition of ADF/cofilin abolishes AMPAR addition. Our data further show that cLTP elicits a temporal sequence of ADF/cofilin dephosphorylation and phosphorylation that underlies AMPAR trafficking and spine enlargement. These findings suggest a novel role for temporally-regulated ADF/cofilin activities in postsynaptic modifications of receptor number and spine size during synaptic plasticity.
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