Spatial and temporal regulation of Ca2+/calmodulin-dependent protein kinase II activity in developing neurons.

We have studied Ca2+/calmodulin-dependent protein kinase II (CaMKII) isoform distribution and activity in embryonic hippocampal neurons developing in culture. We have found that expression of the _ subunit of the enzyme is essential for depolarization-dependent phosphorylation, which in young neurons is limited to the somato-dendritic pool of the kinase. The lack of responsiveness of the axons of young _CaMKII-positive neurons is not due to a lower Ca2+ influx, but rather to a differential balance between kinase and phosphatase activities in this compartment. After the establishment of synaptic contacts, the presynaptic pool of the kinase displays an increasing level of activity and acquires the parallel ability to phosphorylate synapsin I, which represents one of the major CaMKII presynaptic targets in mature nerve terminals. In contrast, the activity of the post-synaptic pool of the kinase remains constant throughout synaptogenesisis. In the presence of a nearly homogeneous subcellular distribution, this highly regionalized regulation of activity may reflect the multi-functional roles of CaMKII in both developing and mature neurons.