PKC epsilon facilitates recovery of exocytosis after an exhausting stimulation.

It has been well documented that protein kinase Cs (PKCs) play multifaceted roles in regulating exocytosis of neurotransmitters and hormones. But the isoform-specific PKC effects are still poorly elucidated mainly because of the large variety of PKC isoforms and the dubious specificity of the commonly used pharmacological agents. In the present study, based on overexpression of wild-type or dominant negative PKC epsilon, we demonstrate in neuroendocrine PC12 cells that PKC epsilon, but not PKC alpha, facilitates recovery of exocytosis after an exhausting stimulation. Specifically, PKC epsilon mediates fast recovery of the extent of exocytosis in a phosphatidylinositol biphosphate-dependent manner, likely through enhancing the rate of vesicle delivery and reorganization of cortical actin network. In addition, PKC epsilon promotes fast recovery of vesicle release kinetics that is slowed after a strong stimulation. These experimental results may suggest a PKC-dependent mechanism relevant to the short-term plasticity of exocytosis in both neurons and neuroendocrine cells.