Assemblies of calcium/calmodulin-dependent kinase II with actin and their dynamic regulation by calmodulin in dendritic spines
Assemblies of calcium/calmodulin-dependent kinase II with actin and their dynamic regulation by calmodulin in dendritic spines
复制标题
DOI：
10.1073/pnas.1911452116
复制
发表时间：
2019-09-17
影响因子：
11.1
通讯作者：
Cheung，Margaret S.
中科院分区：
文献类型：
--
作者：
Wang，Qian;Chen，Mingchen;Cheung，Margaret S.
钙/钙调素依赖性激酶II （CaMKII）在树突棘的可塑性中起关键作用。钙信号导致钙-钙调蛋白激活CaMKII，从而导致脊柱中肌动蛋白丝（F-actin）网络的重塑。我们通过计算机模拟、蛋白质阵列实验和电子显微镜成像相结合的方法阐明了重塑的机制，得出了CaMKII与F-actin的十二聚体复合物的结构模型。绑定接口涉及多个CaMKII域。这种结构解释了由CaMKII的多价性产生的微米级CaMKII/ f -肌动蛋白束的结构。我们还发现CaMKII的调控结构域可以结合钙调蛋白或f -肌动蛋白，但不能同时结合两者。这种挫折，加上结合界面的多部分性质，允许钙调蛋白瞬间从肌动蛋白组装中剥离CaMKII，使它们能够重组。因此，这一观察结果提供了一个简单的机制，通过CaMKII的结构动力学建立钙信号和树突棘形态可塑性之间的联系。
Calcium/calmodulin-dependent kinase II (CaMKII) plays a key role in the plasticity of dendritic spines. Calcium signals cause calcium−calmodulin to activate CaMKII, which leads to remodeling of the actin filament (F-actin) network in the spine. We elucidate the mechanism of the remodeling by combining computer simulations with protein array experiments and electron microscopic imaging, to arrive at a structural model for the dodecameric complex of CaMKII with F-actin. The binding interface involves multiple domains of CaMKII. This structure explains the architecture of the micrometer-scale CaMKII/F-actin bundles arising from the multivalence of CaMKII. We also show that the regulatory domain of CaMKII may bind either calmodulin or F-actin, but not both. This frustration, along with the multipartite nature of the binding interface, allows calmodulin transiently to strip CaMKII from actin assemblies so that they can reorganize. This observation therefore provides a simple mechanism by which the structural dynamics of CaMKII establishes the link between calcium signaling and the morphological plasticity of dendritic spines.