The role of phosphorylation in F-actin binding domain of CaMKII in structural and functional plasticity

在本项目中，我们在CaMKIIβ的肌动蛋白结合域中发现了18个新的磷酸化位点。它们通过亚基间的方式被磷酸化，它们的磷酸化在CaMKIIβ的脊椎定位和F-肌动蛋白捆绑中起着重要的作用。利用生化方法，我们证明了CaMKIIβ介导的F-肌动蛋白结合稳定了F-肌动蛋白，它不仅抑制了肌动蛋白与其调节蛋白之间的相互作用，而且还抑制了它们对肌动蛋白的活性。它具有体内相关性，因此抗磷突变形式的CaMKIIβ既能抑制谷氨酸去势引起的脊髓增大，也能抑制电生理学方法测得的大鼠海马片的长时程增强。

In this project, we identified 18 new phosphorylation sites in actin-binding domain of CaMKIIβ. They are phosphorylated via inter-subunit manner and their phosphorylation is important in spine localization and F-actin bundling of CaMKIIβ. Using biochemical methods, we showed that CaMKIIβ-mediated F-actin bundling stabilizes F-actin and it inhibits the not only interactions between actin and its regulator proteins, but also their activities against actin. It has in vivo relevance so that phosphor-resistant mutant form of CaMKIIβsuppresses both enlargement of a spine induced by glutamate uncaging and LTP measured with electrophysiological method in rat hippocampal slices.