The Association of Vesicular Contents and Its Effects on Release (original) (raw)
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ATP: The crucial component of secretory vesicles
Proceedings of the National Academy of Sciences of the United States of America, 2016
The colligative properties of ATP and catecholamines demonstrated in vitro are thought to be responsible for the extraordinary accumulation of solutes inside chromaffin cell secretory vesicles, although this has yet to be demonstrated in living cells. Because functional cells cannot be deprived of ATP, we have knocked down the expression of the vesicular nucleotide carrier, the VNUT, to show that a reduction in vesicular ATP is accompanied by a drastic fall in the quantal release of catecholamines. This phenomenon is particularly evident in newly synthesized vesicles, which we show are the first to be released. Surprisingly, we find that inhibiting VNUT expression also reduces the frequency of exocytosis, whereas the overexpression of VNUT drastically increases the quantal size of exocytotic events. To our knowledge, our data provide the first demonstration that ATP, in addition to serving as an energy source and purinergic transmitter, is an essential element in the concentration o...
©P. Thorn 2009 Secretory control: evidence for agonist-regulation of post-fusion vesicle behaviour
2015
1. Here we review recent work on vesicular secretion, with a focus on the control of post-fusion events as a means of regulating secretory output. 2. In the classical model of secretion each fused vesicle releases the entirety of its content in an all-or-none manner. In this way the secretory output of a cell is controlled by regulating the numbers of fused vesicles. The realization that post-fusion events can control secretory output leads to a distinct model of partial release of vesicle content. 3. Recent work shows that post-fusion events are under cellular control. Further, new data from our laboratory demonstrates agonist-dependent regulation of fusion pore behaviour. 4. We conclude that post-fusion events are not epiphenomena but are likely an important mechanism of secretory control.
The Journal of physiology, 2002
Trapping of weak bases was utilized to evaluate stimulus-induced changes in the internal pH of the secretory vesicles of chromaffin cells and enteric neurons. The internal acidity of chromaffin vesicles was increased by the nicotinic agonist 1,1-dimethyl-4-phenyl-piperazinium iodide (DMPP; in vivo and in vitro) and by high K+ (in vitro); and in enteric nerve terminals by exposure to veratridine or a plasmalemmal [Ca2+]o receptor agonist (Gd3+). Stimulation-induced acidification of chromaffin vesicles was [Ca2+]o-dependent and blocked by agents that inhibit the vacuolar proton pump (vH+-ATPase) or flux through Cl- channels. Stimulation also increased the average volume of chromaffin vesicles and the proportion that displayed a clear halo around their dense cores (called active vesicles). Stimulation-induced increases in internal acidity and size were greatest in active vesicles. Stimulation of chromaffin cells in the presence of a plasma membrane marker revealed that membrane was int...