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.