The role of CaMKII as an F-actin-bundling protein crucial for maintenance of dendritic spine structure
The role of CaMKII as an F-actin-bundling protein crucial for maintenance of dendritic spine structure
复制标题
DOI：
10.1073/pnas.0701656104
复制
发表时间：
2007-04-10
影响因子：
11.1
通讯作者：
Hayashi, Yasunori
中科院分区：
文献类型：
--
作者：
Okamoto, Ken-Ichi;Narayanan, Radhakrishnan;Hayashi, Yasunori
Ca 2 +-钙调蛋白依赖性蛋白激酶11（CaMKII）是一种丝氨酸/苏氨酸蛋白激酶，在脑中与突触可塑性密切相关。它高度集中在突触后密度部分，超过任何其他信号转导分子的量。由于激酶信号可以通过催化反应放大，CaMKII为何大量存在一直是个谜。在这里，我们提供的生化证据表明，CaMKII是能够捆绑F-肌动蛋白通过化学计量的相互作用。与这一证据相一致，在海马神经元中，RNAi介导的CaMKII下调导致树突棘头部体积减少，这是由F-肌动蛋白动力学介导的。CaMKII的过度表达减缓了脊柱头部的肌动蛋白周转。这种活性与CaMKII的13个亚基相关，需要其肌动蛋白结合和结合结构域，但不需要激酶结构域。这一发现表明，CaMKII作为一个中央信号分子在突触可塑性的功能和结构的变化。
Ca2+-calmodulin-dependent protein kinase 11 (CaMKII) is a serine/ threonine protein kinase critically involved in synaptic plasticity in the brain. It is highly concentrated in the postsynaptic density fraction, exceeding the amount of any other signal transduction molecules. Because kinase signaling can be amplified by catalytic reaction, why CaMKII exists in such a large quantity has been a mystery. Here, we provide biochemical evidence that CaMKII is capable of bundling F-actin through a stoichiometric interaction. Consistent with this evidence, in hippocampal neurons, RNAi-mediated down-regulation of CaMKII leads to a reduction in the volume of dendritic spine head that is mediated by F-actin dynamics. An overexpression of CaMKII slowed down the actin turnover in the spine head. This activity was associated with 13 subunit of CaMKII in a manner requiring its actin-binding and association domains but not the kinase domain. This finding indicates that CaMKII serves as a central signaling molecule in both functional and structural changes during synaptic plasticity.