Toward a unified picture of the exocytotic fusion pore.

Toward a unified picture of the exocytotic fusion pore.
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DOI:
10.1002/1873-3468.13270
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发表时间:
2018-11
期刊:
影响因子:
3.5
通讯作者:
Karatekin E
Karatekin E
中科院分区:
生物学3区
文献类型:
--
作者:
Karatekin E

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神经递质和激素的释放涉及钙触发的融合的货物装载囊泡与质膜。融合膜之间的初始连接,称为融合孔,可以以各种方式进化,包括快速扩张以允许完全释放货物,缓慢扩张,重复打开-关闭和重新密封。孔隙动力学决定了货物释放的动力学和囊泡循环的模式,但这些过程是如何控制的知之甚少。以前的重建不能监测单个孔隙,限制了他们可以提供的机械洞察力。最近开发的基于纳米盘的融合测定允许以前所未有的细节重建和监测单个孔,并为未来的发现带来了巨大的希望。它们概括了胞吐融合孔的各个方面,但比较是困难的,因为不同的方法表明非常不同的胞吐融合孔性质,即使是相同的细胞类型。在这篇评论中,我讨论了如何大部分的数据可以调和,通过认识到不同的方法如何探测同一融合过程的不同方面。由此产生的图片是,融合孔具有广泛分布的属性所产生的随机过程,可以通过蛋白质,脂质和膜施加的物理约束进行调制。
Neurotransmitter and hormone release involve calcium-triggered fusion of a cargo-loaded vesicle with the plasma membrane. The initial connection between the fusing membranes, called the fusion pore, can evolve in various ways, including rapid dilation to allow full cargo release, slow expansion, repeated opening-closing, and resealing. Pore dynamics determine the kinetics of cargo release and the mode of vesicle recycling, but how these processes are controlled are poorly understood. Previous reconstitutions could not monitor single pores, limiting mechanistic insight they could provide. Recently developed nanodisc-based fusion assays allow reconstitution and monitoring of single pores with unprecedented detail and hold great promise for future discoveries. They recapitulate various aspects of exocytotic fusion pores, but comparison is difficult because different approaches suggested very different exocytotic fusion pore properties, even for the same cell type. In this Review, I discuss how most of the data can be reconciled, by recognizing how different methods probe different aspects of the same fusion process. The resulting picture is that fusion pores have broadly distributed properties arising from stochastic processes which can be modulated by physical constraints imposed by proteins, lipids and membranes.
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