Regulation of protein kinase C isozymes during early postnatal hippocampal development.

During neonatal hippocampal development, serotonin 1A receptor-mediated signaling initially employs PKCepsilon to boost neuronal proliferation and then uses PKCalpha to promote synaptogenesis. Such stage-specific involvement of a PKC isozyme could be determined by its relative expression level. In mouse hippocampi, we detected relatively low levels of alpha, beta, gamma, and delta isozymes at postnatal days 2-6 (P2-6), which was followed by a large increase in their expression. In contrast, the PKC isozymes epsilon and theta were relatively abundant at P6, following which they underwent a further increase by P15. Comparison with purified proteins confirmed that the PKCepsilon levels at P6 and P15 were respectively 1.75 and 7.36 ng per 60 microg of protein, whereas PKCalpha levels at P6 and P15 were respectively 160 pg and 1.186 ng per 60 microg of protein. Therefore, at P6, PKCepsilon was about 11-fold more abundant than PKCalpha. Consequently, signaling cascades could use the relatively abundant PKCepsilon (and possibly PKCtheta) molecules for early events at P2-6 (e.g. neurogenesis), following which PKCalpha (and the beta, gamma, or delta isozymes) could guide maturation or apoptosis. Notably, at P6 but not P15, PKCepsilon, was localized to the nuclei of neuroblasts, probably directing mitosis. In contrast, at P15 but not P6, PKCalpha was highly expressed in the processes of the differentiated hippocampal neurons. In summary, PKC isozymes follow differential profiles of expression in neonatal hippocampus and the relative abundance of each may determine its mode and stage of involvement in hippocampal development.