RT Journal Article SR Electronic T1 Involvement of Protein Kinase C-ε in Activity-Dependent Potentiation of Large Dense-Core Vesicle Exocytosis in Chromaffin Cells JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 8999 OP 9005 DO 10.1523/JNEUROSCI.2828-06.2006 VO 26 IS 35 A1 Park, Yong-Soo A1 Hur, Eun-Mi A1 Choi, Bo-Hwa A1 Kwak, Eunyee A1 Jun, Dong-Jae A1 Park, Su-Jin A1 Kim, Kyong-Tai YR 2006 UL http://www.jneurosci.org/content/26/35/8999.abstract 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.