A Temporary Gating of Actin Remodeling during Synaptic Plasticity Consists of the Interplay between the Kinase and Structural Functions of CaMKII.
A Temporary Gating of Actin Remodeling during Synaptic Plasticity Consists of the Interplay between the Kinase and Structural Functions of CaMKII.
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DOI：
10.1016/j.neuron.2015.07.023
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发表时间：
2015-08-19
期刊：
影响因子：
16.2
通讯作者：
Okamoto K
中科院分区：
文献类型：
--
作者：
Kim K;Lakhanpal G;Lu HE;Khan M;Suzuki A;Hayashi MK;Narayanan R;Luyben TT;Matsuda T;Nagai T;Blanpied TA;Hayashi Y;Okamoto K
树突棘的结构修饰在突触可塑性中起着关键作用。CaMKII是一个关键的分子，通过激酶依赖性和独立的结构功能参与这一过程，但这两种功能对突触可塑性的各自贡献尚不清楚。我们表明，瞬时之间的相互作用的激酶和结构功能的CaMKII在突触可塑性的诱导时间门的肌动蛋白细胞骨架的活性依赖性的修改。非活性CaMKII结合F-肌动蛋白，从而限制肌动蛋白调节蛋白接近F-肌动蛋白并稳定棘结构。CaMKII激活刺激通过F-肌动蛋白结合区域内的特异性自磷酸化反应触发CaMKII从F-肌动蛋白解离，并允许调节蛋白重塑F-肌动蛋白，然后重新缔合和重新稳定。阻断自磷酸化损害功能和结构可塑性，而不影响激酶活性。这些结果支持的重要性之间的相互作用的激酶和结构功能的CaMKII在定义一个时间窗口允许突触可塑性。
The structural modification of dendritic spines plays a critical role in synaptic plasticity. CaMKII is a pivotal molecule involved in this process through both kinase-dependent and independent structural functions, but the respective contributions of these two functions to the synaptic plasticity remain unclear. We demonstrate that the transient interplay between the kinase and structural functions of CaMKII during the induction of synaptic plasticity temporally gates the activity-dependent modification of the actin cytoskeleton. Inactive CaMKII binds F-actin, thereby limiting access of actin regulating proteins to F-actin and stabilizing spine structure. CaMKII-activating stimuli trigger dissociation of CaMKII from F-actin through specific autophosphorylation reactions within the F-actin binding region and permits F-actin remodeling by regulatory proteins followed by reassociation and restabilization. Blocking the autophosphorylation impairs both functional and structural plasticity without affecting kinase activity. These results underpin the importance of the interplay between the kinase and structural functions of CaMKII in defining a time window permissive for synaptic plasticity.