Differential involvement of protein kinase C alpha and epsilon in the regulated secretion of soluble amyloid precursor protein

We investigated the differential role of protein kinase C (PKC) isoforms in the regulated proteolytic release of soluble amyloid precursor protein (sAPPa) in SH-SY5Y neuroblastoma cells. We used cells stably transfected with cDNAs encoding either PKCa or PKCe in the antisense orientation, producing a reduction of the expression of PKCa and PKCe, respectively. Reduced expression of PKCa and/or PKCe did not modify the response of the kinase to phorbol ester stimulation, demonstrating translocation of the respective isoforms from the cytosolic fraction to specific intracellular compartments with an interesting differential localization of PKCa to the plasma membrane and PKCe to Golgi-like structures. Reduced expression of PKCa significantly impaired the secretion of sAPPa induced by treatment with phorbol esters. Treatment of PKCadeficient cells with carbachol induced a significant release of sAPPa. These results suggest that the involvement of PKCa in carbachol-induced sAPPa release is negligible. The response to carbachol is instead completely blocked in PKCe-deficient cells suggesting the importance of PKCe in coupling cholinergic receptors with APP metabolism.