Involvement of Protein Kinase C-ε in Activity-Dependent Potentiation of Large Dense-Core Vesicle Exocytosis in Chromaffin Cells

Park, Yong Soo; Hur, Eun Mi; Choi, Bo-Hwa; Kwak, Eunyee; Jun, Dong-Jae; Park, Su‐Jin; Kim, Kyong‐Tai

doi:10.1523/jneurosci.2828-06.2006

Cited by 44 publications

(71 citation statements)

References 42 publications

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“…3). It seems, therefore, that the well characterized effect of PKC on the RRP in chromaffin cells is more important for activity-dependent than for receptormediated potentiation of exocytosis (Smith, 1999;Park et al, 2006). We cannot dismiss a possible PKC-mediated modulation of the fusion pore, because this would not necessarily be apparent in C m measurements.…”

Section: Discussionmentioning

confidence: 93%

Potentiation of Exocytosis by Phospholipase C-Coupled G-Protein-Coupled Receptors Requires the Priming Protein Munc13-1

Bauer¹,

Woolley²,

Teschemacher³

et al. 2007

J. Neurosci.

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The vesicle priming protein Munc13-1 is regulated by diacylglycerol (DAG) and is therefore hypothesized to play a role in the control of neurotransmitter release by phospholipase C (PLC)-coupled receptors. We combined voltage-clamp recordings of voltage-gated Ca 2ϩ channels (VGCCs) and high-resolution capacitance measurements to investigate the mechanism of receptor-mediated modulation of exocytosis in bovine chromaffin cells. Activation of endogenous H 1 G q -protein-coupled receptors (G q PCRs) by histamine potentiated stimulus-coupled secretion despite concurrently inhibiting Ca 2ϩ influx through VGCCs. Histamine increased the size of the readily releasable pool of vesicles and in particular a subpool of fusion-competent vesicles localized in close proximity to VGCCs. Pharmacological characterization showed that potentiation of exocytosis depended on the activation of PLC but not protein kinase C. Overexpression of wild-type Munc13-1 by adenoviral infection had no effect on histamine-induced potentiation per se, whereas DAG-insensitive Munc13-1 H567K completely abolished it. This is the first endogenous mammalian G q PCR signaling pathway identified that engages Munc13-1 to increase stimulus-coupled secretion by recruiting vesicles to the immediately releasable pool. G q PCRs are therefore able to control exocytosis at the level of SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex formation to produce rapid, short-term potentiation of the secretory output of neurons and endocrine cells.

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Section: Discussionmentioning

confidence: 93%

Potentiation of Exocytosis by Phospholipase C-Coupled G-Protein-Coupled Receptors Requires the Priming Protein Munc13-1

Bauer¹,

Woolley²,

Teschemacher³

et al. 2007

J. Neurosci.

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show abstract

“…Several lines of evidences have been documented that PKC activation (e.g., by PMA) causes disassembly and reorganization of dense actin cortex clearing the way for myosindependent transport of vesicles from the reserve pool to the plasma membrane along the remaining fine actin filament [41]. PKC activation disrupts and reorganizes actin networks probably through multiple pathways, including recruitment of actin severing protein scinderin [40] and phosphorylation of MARCKS [19,41] or phosphorylation of other actin-filament-associated proteins [20]. It explains our observation that PMA largely increased the traffic between the reserved vesicle pool and docked vesicle pool.…”

Section: Discussionmentioning

confidence: 99%

“…Its phosphorylation enhances vesicle replenishment likely via inhibiting the association of Munc18 with syntaxin and consequently increasing free syntaxin for SNARE complex formation [17]. Furthermore, activation of PKC causes disassembly of peripheral F-actin cytoskeleton and thus facilities vesicle access to the plasma membrane [18], likely via phosphorylation of MARCK [19] or other actinfilament-associated proteins [20]. More recently, it has been revealed that in parallel to its classic action on PKC, DAG also binds with Munc13 and consequently induces augmentation of exocytosis [21].…”

Section: Introductionmentioning

confidence: 99%

Effects of phorbol ester on vesicle dynamics as revealed by total internal reflection fluorescence microscopy

Zhang

Xue

Soo

et al. 2008

Pflugers Arch - Eur J Physiol

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Exocytosis of neurotransmitter or hormone-filled vesicles is a highly dynamic process regulated by various proteins and lipids. As mainly revealed indirectly by the electrophysiological methods, exocytosis is believed to involve multiple kinetic steps in which vesicles transit from one state to another. Using total internal reflection fluorescence microscopy which enables direct visualization of individual vesicles, we developed an analytical framework to track and analyze vesicle dynamics. We demonstrated that all subplasmalemmal vesicles generally undergo constant and caged Brownian motion. And they can be classified into three populations that differ in their motion characteristics and fusion competence. Furthermore, we showed that these vesicle pools are differentially modulated by phorbol-12-myristate-13-acetate, a phorbol ester analog to endogenous diacylglycerol, through both protein-kinase-C-dependent and -independent pathways.

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“…It has been shown that it facilitates activitydependent potentiation in bovine chromaffin cells [35] and synaptic potentiation in rat nerve terminal [38]. We herein investigate the roles of PKCε in recovering exocytosis.…”

Section: Resultsmentioning

confidence: 97%

PKC epsilon facilitates recovery of exocytosis after an exhausting stimulation

Xue

Zhao

et al. 2009

Pflugers Arch - Eur J Physiol

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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.

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Involvement of Protein Kinase C-ε in Activity-Dependent Potentiation of Large Dense-Core Vesicle Exocytosis in Chromaffin Cells

Cited by 44 publications

References 42 publications

Potentiation of Exocytosis by Phospholipase C-Coupled G-Protein-Coupled Receptors Requires the Priming Protein Munc13-1

Potentiation of Exocytosis by Phospholipase C-Coupled G-Protein-Coupled Receptors Requires the Priming Protein Munc13-1

Effects of phorbol ester on vesicle dynamics as revealed by total internal reflection fluorescence microscopy

PKC epsilon facilitates recovery of exocytosis after an exhausting stimulation

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