Protein kinase C delta regulates neural cell adhesion molecule polysialylation state in the rat brain

Polysialylation of neural cell adhesion molecule (NCAM PSA) modulates cell-cell hemophilic binding and signalling during brain development and the remodelling of discrete brain regions in the adult. Following learning, a transient increase in the frequency of polysialylated neurones occurs in the dentate gyrus of the hippocampal formation, and this has been correlated with the selective retention and/or elimination of synapses that are transiently overproduced during memory consolidation. We now demonstrate that protein kinase C delta (PKC delta) negatively regulates polysialyltransferase activity in the rat brain during development and also in the hippocampus during memory consolidation, where its downregulation in the Golgi membrane fraction coincides with the transient increase in NCAM PSA expression. Decreased expression of PKC delta was also observed in the hippocampus of rats reared in a complex environment and this directly contrasted the significant increase in frequency of hippocampal polysialylated neurones observed in these animals. These effects were isoform-specific as no change in total PKC enzyme activity was detected during memory consolidation and complex environment rearing had no effect on the hippocampal expression of PKC alpha, beta, gamma or epsilon. By sequential immunoprecipitation and immunoblot analysis, phosphorylation of polysialyltransferase protein(s) was (were) demonstrated to occur on both serine and tyrosine residues and this was associated with decreased enzyme activity. Moreover, a similar experimental approach revealed the degree of PKC delta co-precipitation with polysialyltransferase protein(s) to be inversely correlated with polysialyltransferase activity. These findings support in vitro evidence indicating PKC delta to regulate polysialyltransferase activity and NCAM polysialylation state.