Targeting mechanisms for calmodulin-dependent protein kinases and their neuronal functions

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The aim of this project is to clarify the neuronal functions of calmodulin-dependent protein kinases, particularly CaM kinase I (CaMKI). To obtain better understanding of the functions of CaMKI, we first examined the developmental expression of the four isoform (a, b2, g, d) in mouse brain by in situ hybridization histochemistry. In the developing hippocampus, the four isoforms of CaMKI exhibit distinct expression patterns in terms of the chronological order of the appearance in the hippocampal subregions. For example, CaMKIδ, which is the most abundant isoform in the hippocampal pyramidal neurons, started to be expressed in the CA3 regions, followed by the CA1. On the other hand, the expression of CaMKIα and CaMKIβ2 is decreased after the postnatal second week in the hippocampal pyramidal cell layer. Since the temporal expression patterns of CaMKIs, particularly CaMKIδ, correlates well with the temporal schedule of the dendritic formation of the hippocampal pyramidal neurons, we examined the functional involvement of CaMKI in the deridritic formation of cultured hippocampal neurons by transfecting various kinase-dead mutants of CaMKI which were expected to work as dominant negatives. The overexpression of kinase-dead mutants of CaMKI reduced the average dendritic length of the transfected neurons without any significant effects on the number of primary dendrites and branching index. This finding suggest that CaMKI may be involved in the dendritic growth, particularly the extension of dendrites.