Activity-dependent modulation of the interaction between CaMKIIα and Abil and its involvement in Spine maturation

Abstract

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 Ha (Abil -CaMKIIα) interaction, and thereby their activity, is important for regulation of spine morphology in cultured rat hippocampal neurons. Abil interacts with CaMKIIα at resting conditions through Abil's tSNARE (target membrane-associated SNARE), which harbors striking homology with CaMKIIα regulatory domain. The interaction of the two proteins, Abil and CaMKIIα, results in their simultaneous inhibition, inhibition of CaMKIIα activity, and also inhibition of Abil-dependent Rac activation. Their functional impediment is released when they dissociate from each other by calmodulin binding through glutamate receptor activation. Before dissociation, Abil 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 Abil and CaMKIIα, through the glutamate receptor pathway, may be a molecular mechanism underlying activity-regulated structural plasticity in rat hippocamapal neurons. © 2012 the authors.