PT - JOURNAL ARTICLE AU - Park, Yong-Soo AU - Hur, Eun-Mi AU - Choi, Bo-Hwa AU - Kwak, Eunyee AU - Jun, Dong-Jae AU - Park, Su-Jin AU - Kim, Kyong-Tai TI - Involvement of Protein Kinase C-ε in Activity-Dependent Potentiation of Large Dense-Core Vesicle Exocytosis in Chromaffin Cells AID - 10.1523/JNEUROSCI.2828-06.2006 DP - 2006 Aug 30 TA - The Journal of Neuroscience PG - 8999--9005 VI - 26 IP - 35 4099 - http://www.jneurosci.org/content/26/35/8999.short 4100 - http://www.jneurosci.org/content/26/35/8999.full SO - J. Neurosci.2006 Aug 30; 26 AB - Neurotransmitter release is modulated in an activity-dependent manner. We showed previously that repetitive stimulation of nicotinic acetylcholine receptor (nAChR) induced activity-dependent potentiation (ADP) of large dense-core vesicle (LDCV) exocytosis in chromaffin cells. Here we report that protein kinase C (PKC)-ε is critically involved in ADP. Stimulation of nAChR induced activation of PKC-ε, and inhibition of PKC-ε by expression of the dominant-negative mutant of PKC-ε (DN-PKC-ε) or short interfering (siRNA) against PKC-ε abolished ADP via decreasing the frequency and quantal size of fused vesicles without affecting basal exocytosis, suggesting that PKC-ε is specifically involved in ADP. Electron microscopy revealed that inhibition of PKC-ε disrupts activity-induced vesicle translocation required for ADP. We also suggest the involvement of myristoylated alanine-rich C kinase substrate (MARCKS), which is known as a downstream target of PKC-ε, in ADP of LDCV exocytosis. The level of phospho-MARCKS correlated with the time course of ADP and was reduced by transfection with DN-PKC-ε. Actin filament disassembly induced by MARCKS phosphorylation was also significantly blocked by transfection of DN-PKC-ε. Furthermore, knockdown of MARCKS by siRNA resulted in inhibition of ADP and reduction of the number of fused vesicles. Together, we provide evidence that ADP of LDCV exocytosis is regulated by PKC-ε and its downstream target MARCKS via modulating vesicle translocation.