Selective Regulation of Neurite Extension and Synapse Formation by the β but not the α Isoform of CaMKII

Abstract

Neurite extension and branching are important neuronal plasticity mechanisms that can lead to the addition of synaptic contacts in developing neurons and changes in the number of synapses in mature neurons. Here we show that Ca 2+/calmodulin-dependent protein kinase II (CaMKII) regulates movement, extension, and branching of filopodia and fine dendrites as well as the number of synapses in hippocampal neurons. Only CaMKIIβ, which peaks in expression early in development, but not CaMKIIα, has this morphogenic activity. A small insert in CaMKIIβ, which is absent in CaMKIIα, confers regulated F-actin localization to the enzyme and enables selective upregulation of dendritic motility. These results show that the two main neuronal CaMKII isoforms have markedly different roles in neuronal plasticity, with CaMKIIα regulating synaptic strength and CaMKIIβ controlling the dendritic morphology and number of synapses .