ATP: The crucial component of secretory vesicles
ATP: The crucial component of secretory vesicles
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DOI：
10.1073/pnas.1600690113
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发表时间：
2016-07-12
影响因子：
11.1
通讯作者：
David Machado, Jose
中科院分区：
文献类型：
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作者：
Estevez-Herrera, Judith;Dominguez, Natalia;David Machado, Jose
体外证明的 ATP 和儿茶酚胺的依数特性被认为是嗜铬细胞分泌囊泡内溶质异常积累的原因，尽管这尚未在活细胞中得到证实。由于功能细胞不能剥夺 ATP，因此我们降低了囊泡核苷酸载体 VNUT 的表达，以表明囊泡 ATP 的减少伴随着儿茶酚胺释放量的急剧下降。这种现象在新合成的囊泡中尤其明显，我们证明它们是第一个被释放的。令人惊讶的是，我们发现抑制 VNUT 表达也会降低胞吐作用的频率，而 VNUT 的过度表达会大大增加胞吐事件的量子大小。据我们所知，我们的数据首次证明 ATP 除了作为能量来源和嘌呤能递质外，还是分泌囊泡中儿茶酚胺浓度的重要元素。通过这种方式，细胞可以利用 ATP 积累高浓度的神经递质和其他分泌物质，支持量子传输。
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 of catecholamines in secretory vesicles. In this way, cells can use ATP to accumulate neurotransmitters and other secreted substances at high concentrations, supporting quantal transmission.