Regulation of Exocytotic Fusion Pores by SNARE Protein Transmembrane Domains.
Regulation of Exocytotic Fusion Pores by SNARE Protein Transmembrane Domains.
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DOI：
10.3389/fnmol.2017.00315
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发表时间：
2017
影响因子：
4.8
通讯作者：
Karatekin E
中科院分区：
文献类型：
--
作者：
Wu Z;Thiyagarajan S;O'Shaughnessy B;Karatekin E
钙触发的神经递质和激素从神经元和神经内分泌细胞的胞吐释放是神经元通信、运动活动和内分泌功能的基础。神经元胞吐机制的核心是可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）。囊泡附着的v-和质膜锚定的t-SNARE之间以高度调节的方式形成复合物，使膜紧密贴壁。称为复合蛋白（Cpx）的小的可溶性蛋白质和钙敏感的突触结合蛋白（Synaptotagmins）在低静息钙浓度下合作阻断融合，但在钙增加时触发释放。越来越多的证据表明，SNARE蛋白的跨膜结构域（TMD）在调节融合和释放过程中发挥重要作用，但所涉及的机制才刚刚开始被发现。在这里，我们回顾了最近的证据表明，SNARE TMDs通过调节融合孔的动力学发挥影响，融合孔是囊泡腔和细胞外间隙之间的初始水连接。即使在融合孔建立之后，神经内分泌细胞的激素释放也受到严格控制，神经元的神经递质释放也可能如此。融合孔的动力学可以调节货物释放的动力学和净释放量，并且可以决定囊泡再循环的模式。SNARE TMD的操纵被发现深刻影响融合孔的性质，在胞吐和生化重建。为了解释这些影响，TMD的灵活性，以及TMD之间或TMD和脂质之间的相互作用已被调用。胞吐作用提供了最好的环境，在其中解开潜在的机制，是独特的膜融合反应中，单一的融合孔可以使用高分辨率的方法进行探测。一个重要的作用可能会发挥的方法，可以探测单一的融合孔在一个生物化学定义的设置，最近已成为可用的。最后，计算机模拟是有价值的机械工具，因为它们有能力访问实验无法访问的小长度尺度和非常短的时间。
Calcium-triggered exocytotic release of neurotransmitters and hormones from neurons and neuroendocrine cells underlies neuronal communication, motor activity and endocrine functions. The core of the neuronal exocytotic machinery is composed of soluble N-ethyl maleimide sensitive factor attachment protein receptors (SNAREs). Formation of complexes between vesicle-attached v- and plasma-membrane anchored t-SNAREs in a highly regulated fashion brings the membranes into close apposition. Small, soluble proteins called Complexins (Cpx) and calcium-sensing Synaptotagmins cooperate to block fusion at low resting calcium concentrations, but trigger release upon calcium increase. A growing body of evidence suggests that the transmembrane domains (TMDs) of SNARE proteins play important roles in regulating the processes of fusion and release, but the mechanisms involved are only starting to be uncovered. Here we review recent evidence that SNARE TMDs exert influence by regulating the dynamics of the fusion pore, the initial aqueous connection between the vesicular lumen and the extracellular space. Even after the fusion pore is established, hormone release by neuroendocrine cells is tightly controlled, and the same may be true of neurotransmitter release by neurons. The dynamics of the fusion pore can regulate the kinetics of cargo release and the net amount released, and can determine the mode of vesicle recycling. Manipulations of SNARE TMDs were found to affect fusion pore properties profoundly, both during exocytosis and in biochemical reconstitutions. To explain these effects, TMD flexibility, and interactions among TMDs or between TMDs and lipids have been invoked. Exocytosis has provided the best setting in which to unravel the underlying mechanisms, being unique among membrane fusion reactions in that single fusion pores can be probed using high-resolution methods. An important role will likely be played by methods that can probe single fusion pores in a biochemically defined setting which have recently become available. Finally, computer simulations are valuable mechanistic tools because they have the power to access small length scales and very short times that are experimentally inaccessible.
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DOI：
10.1083/jcb.201311085
发表时间：
2014-03-31
期刊：
The Journal of cell biology
影响因子：
--
作者：
Dhara M;Yarzagaray A;Schwarz Y;Dutta S;Grabner C;Moghadam PK;Bost A;Schirra C;Rettig J;Reim K;Brose N;Mohrmann R;Bruns D
通讯作者：
Bruns D
影响因子：
16.6
作者：
Chiang, Hsueh-Cheng;Shin, Wonchul;Zhao, Wei-Dong;Hamid, Edaeni;Sheng, Jiansong;Baydyuk, Maryna;Wen, Peter J.;Jin, Albert;Momboisse, Fanny;Wu, Ling-Gang
通讯作者：
Wu, Ling-Gang
影响因子：
3.4
作者：
Blanchard, Andrew E.;Arcario, Mark J.;Tajkhorshid, Emad
通讯作者：
Tajkhorshid, Emad
影响因子：
5.3
作者：
Chang, Che-Wei;Hui, Enfu;Jackson, Meyer B.
通讯作者：
Jackson, Meyer B.
影响因子：
2.9
作者：
Durrieu, Marie-Pierre;Bond, Peter J.;Baaden, Marc
通讯作者：
Baaden, Marc