School of Biological Sciences, Seoul National University, Seoul 151-747, South Korea.
J Neurosci. 2012 Sep 19;32(38):13177-88. doi: 10.1523/JNEUROSCI.2257-12.2012.
Remodeling of dendritic spines through regulation of actin dynamics is a key event in activity-dependent structural plasticity. However, the molecular mechanism underlying this process is poorly understood. Here, we show that activity-dependent modulation of Abl interactor 1-Ca(2+)/calmodulin-dependent kinase IIα (Abi1-CaMKIIα) interaction, and thereby their activity, is important for regulation of spine morphology in cultured rat hippocampal neurons. Abi1 interacts with CaMKIIα at resting conditions through Abi1's tSNARE (target membrane-associated SNARE), which harbors striking homology with CaMKIIα regulatory domain. The interaction of the two proteins, Abi1 and CaMKIIα, results in their simultaneous inhibition, inhibition of CaMKIIα activity, and also inhibition of Abi1-dependent Rac activation. Their functional impediment is released when they dissociate from each other by calmodulin binding through glutamate receptor activation. Before dissociation, Abi1 is phosphorylated by CaMKIIα at serine 88, which may involve in regulation of Rac activation and spine maturation. Our results suggest that modulation of the interaction between Abi1 and CaMKIIα, through the glutamate receptor pathway, may be a molecular mechanism underlying activity-regulated structural plasticity in rat hippocamapal neurons.
通过调节肌动蛋白动力学重塑树突棘是活性依赖的结构可塑性的关键事件。然而，这一过程的分子机制还了解甚少。在这里，我们表明，Abl 相互作用蛋白 1-Ca(2+)/钙调蛋白依赖性激酶 IIα（Abi1-CaMKIIα）相互作用的活性依赖性调节，以及它们的活性，对于调节培养的大鼠海马神经元中的棘突形态很重要。在静息状态下，Abi1 通过 Abi1 的 tSNARE（靶膜相关 SNARE）与 CaMKIIα 相互作用，Abi1 的 tSNARE 与 CaMKIIα 的调节域具有显著的同源性。这两种蛋白质（Abi1 和 CaMKIIα）的相互作用导致它们的同时抑制，CaMKIIα 活性的抑制，以及 Abi1 依赖性 Rac 激活的抑制。当它们通过谷氨酸受体激活与钙调蛋白结合彼此解离时，它们的功能障碍就会被释放。在解离之前，CaMKIIα 在丝氨酸 88 处将 Abi1 磷酸化，这可能参与 Rac 激活和棘突成熟的调节。我们的结果表明，通过谷氨酸受体途径调节 Abi1 和 CaMKIIα 之间的相互作用，可能是大鼠海马神经元中活性调节结构可塑性的分子机制。
