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 rem odelling of discrete brain regions in the adult. Following learning, a tran sient increase in the frequency of polysialylated neurones occurs in the de ntate gyrus of the hippocampal formation, and this has been correlated with the selective retention and/or elimination of synapses that are transientl y overproduced during memory consolidation. We now demonstrate that protein kinase C delta (PKC delta) negatively regulates polysialyltransferase acti vity in the rat brain during development and also in the hippocampus during memory consolidation, where its downregulation in the Golgi membrane fract ion coincides with the transient increase in NCAM PSA expression. Decreased expression of PKC delta was also observed in the hippocampus of rats reare d in a complex environment and this directly contrasted the significant inc rease in frequency of hippocampal polysialylated neurones observed in these animals. These effects were isoform-specific as no change in total PKC enz yme activity was detected during memory consolidation and complex environme nt 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) demonstrat ed to occur on both serine and tyrosine residues and this was associated wi th decreased enzyme activity. Moreover, a similar experimental approach rev ealed the degree of PKC delta co-precipitation with polysialyltransferase p rotein(s) to be inversely correlated with polysialyltransferase activity. T hese findings support in vitro evidence indicating PKC delta to regulate po lysialyltransferase activity and NCAM polysialylation state.