Regulation of large dense-core vesicle volume and neurotransmitter content mediated by adaptor protein 3

Regulation of large dense-core vesicle volume and neurotransmitter content mediated by adaptor protein 3
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DOI:
10.1073/pnas.0509844103
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发表时间:
2006-06-27
影响因子:
11.1
通讯作者:
Fox, Aaron P.
Fox, Aaron P.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Grabner, Chad P.;Price, Steven D.;Fox, Aaron P.

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接合蛋白3(AP-3)是一种囊泡-外壳蛋白,形成异四聚体复合体。在哺乳动物细胞中发现两种类型的AP-3亚单位。AP-3亚基普遍存在于人体的所有组织中,包括大脑。此外,还有神经元AP-3亚单位,被认为具有神经元特有的功能,如神经递质释放。在这项研究中,我们发现,在小鼠嗜铬细胞中过表达神经元AP-3会导致单个小泡的神经递质含量(量子大小)显著减少,而所有AP-3的缺失会导致量子大小的急剧增加;这些变化与致密核小泡大小的变化有关。AP-3似乎定位于跨高尔基体网络和可能未成熟的分泌囊泡中,在那里它可能参与神经分泌囊泡的形成。
Adaptor protein 3 (AP-3) is a vesicle-coat protein that forms a heterotetrameric complex. Two types of AP-3 subunits are found in mammalian cells. Ubiquitous AP-3 subunits are expressed in all tissues of the body, including the brain. In addition, there are neuronal AP-3 subunits that are thought to serve neuron-specific functions such as neurotransmitter release. In this study, we show that overexpression of neuronal AP-3 in mouse chromaffin cells results in a striking decrease in the neurotransmitter content of individual vesicles (quantal size), whereas deletion of all AP-3 produces a dramatic increase in quantal size; these changes were correlated with alterations in dense-core vesicle size. AP-3 appears to localize in the trans-Golgi network and possibly immature secretory vesicles, where it may be involved in the formation of neurosecretory vesicles.