Activity-Dependent Modulation of the Interaction between CaMKIIα and Abi1 and Its Involvement in Spine Maturation

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-Ca2+/calmodulin-dependent kinase II alpha (Abi1-CaMKII alpha) interaction, and thereby their activity, is important for regulation of spine morphology in cultured rat hippocampal neurons. Abi1 interacts with CaMKII alpha at resting conditions through Abi1's tSNARE (target membrane-associated SNARE), which harbors striking homology with CaMKII alpha regulatory domain. The interaction of the two proteins, Abi1 and CaMKII alpha, results in their simultaneous inhibition, inhibition of CaMKII alpha 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 CaMKII alpha 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 CaMKII alpha, through the glutamate receptor pathway, may be a molecular mechanism underlying activity-regulated structural plasticity in rat hippocamapal neurons.