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

2006 ◽  
Vol 26 (35) ◽  
pp. 8999-9005 ◽  
Author(s):  
Y.-S. Park
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Chromaffin Cells ◽  
Dense Core ◽  
Dense Core Vesicle ◽  
Large Dense Core Vesicle ◽  
Kinase C ◽  
Vesicle Exocytosis ◽  
Activity Dependent

scholarly journals Identification of a Munc13-sensitive step in chromaffin cell large dense-core vesicle exocytosis

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Kwun Nok M Man ◽  
Cordelia Imig ◽  
Alexander M Walter ◽  
Paulo S Pinheiro ◽  
David R Stevens ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Synaptic Vesicle ◽  
Chromaffin Cells ◽  
Chromaffin Cell ◽  
Dense Core ◽  
Dense Core Vesicle ◽  
Vesicle Docking ◽  
Large Dense Core Vesicle ◽  
Vesicle Exocytosis

It is currently unknown whether the molecular steps of large dense-core vesicle (LDCV) docking and priming are identical to the corresponding reactions in synaptic vesicle (SV) exocytosis. Munc13s are essential for SV docking and priming, and we systematically analyzed their role in LDCV exocytosis using chromaffin cells lacking individual isoforms. We show that particularly Munc13-2 plays a fundamental role in LDCV exocytosis, but in contrast to synapses lacking Munc13s, the corresponding chromaffin cells do not exhibit a vesicle docking defect. We further demonstrate that ubMunc13-2 and Munc13-1 confer Ca2+-dependent LDCV priming with similar affinities, but distinct kinetics. Using a mathematical model, we identify an early LDCV priming step that is strongly dependent upon Munc13s. Our data demonstrate that the molecular steps of SV and LDCV priming are very similar while SV and LDCV docking mechanisms are distinct.

scholarly journals Physiological stimulation regulates the exocytic mode through calcium activation of protein kinase C in mouse chromaffin cells

2006 ◽  
Vol 399 (1) ◽  
pp. 111-119 ◽  
Author(s):  
Tiberiu Fulop ◽  
Corey Smith
Keyword(s):  
Protein Kinase C ◽  
Stress Response ◽  
Protein Kinase ◽  
Chromaffin Cells ◽  
Acute Stress ◽  
Dense Core ◽  
Fusion Pore ◽  
Dependent Manner ◽  
Physiological Regulation ◽  
Kinase C

Adrenal medullary chromaffin cells release catecholamines and neuropeptides in an activity-dependent manner controlled by the sympathetic nervous system. Under basal sympathetic tone, catecholamines are preferentially secreted. During acute stress, increased sympathetic firing evokes release of both catecholamines as well as neuropeptides. Both signalling molecules are co-packaged in the same large dense core granules, thus release of neuropeptide transmitters must be regulated after granule fusion with the cell surface. Previous work has indicated this may be achieved through a size-exclusion mechanism whereby, under basal sympathetic firing, the catecholamines are selectively released through a restricted fusion pore, while less-soluble neuropeptides are left behind in the dense core. Only under the elevated firing experienced during the sympathetic stress response do the granules fully collapse to expel catecholamines and neuropeptides. However, mechanistic description and physiological regulation of this process remain to be determined. We employ electrochemical amperometry, fluid-phase dye uptake and electrophysiological capacitance noise analysis to probe the fusion intermediate in mouse chromaffin cells under physiological electrical stimulation. We show that basal firing rates result in the selective release of catecholamines through an Ω-form ‘kiss and run’ fusion event characterized by a narrow fusion pore. Increased firing raises calcium levels and activates protein kinase C, which then promotes fusion pore dilation until full granule collapse occurs. Our results demonstrate that the transition between ‘kiss and run’ and ‘full collapse’ exocytosis serves a vital physiological regulation in neuroendocrine chromaffin cells and help effect a proper acute stress response.

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