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作为治疗靶点的胞吐融合孔

Exocytotic fusion pores as a target for therapy.

作者信息

Jorgačevski Jernej, Kreft Marko, Zorec Robert

机构信息

Laboratory of Neuroendocrinology-Molecular Cell Physiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia; Celica Biomedical Center, Tehnološki park 24, 1000 Ljubljana, Slovenia.

Laboratory of Neuroendocrinology-Molecular Cell Physiology, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia; Celica Biomedical Center, Tehnološki park 24, 1000 Ljubljana, Slovenia; Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana, Večna pot 111, 1000 Ljubljana, Slovenia.

出版信息

Cell Calcium. 2017 Sep;66:71-77. doi: 10.1016/j.ceca.2017.06.005. Epub 2017 Jun 19.

Abstract

Regulated exocytosis can be split into a sequence of steps ending with the formation and the dilation of a fusion pore, a neck-like connection between the vesicle and the plasma membrane. Each of these steps is precisely controlled to achieve the optimal spatial and temporal profile of the release of signalling molecules. At the level of the fusion pore, tuning of the exocytosis can be achieved by preventing its formation, by stabilizing the unproductive narrow fusion pore, by altering the speed of fusion pore expansion and by completely closing the fusion pore. The molecular structure and dynamics of fusion pores have become a major focus of cell research, especially as a promising target for therapeutic strategies. Electrophysiological, optical and electrochemical methods have been used extensively to illuminate how cells regulate secretion at the level of a single fusion pore. Here, we describe recent advances in the structure and mechanisms of the initial fusion pore formation and the progress in therapeutic strategies with the focus on exocytosis.

摘要

调节性胞吐作用可分为一系列步骤,最终形成并扩张融合孔,融合孔是囊泡与质膜之间类似颈部的连接结构。这些步骤中的每一步都受到精确控制,以实现信号分子释放的最佳时空分布。在融合孔水平上,可通过阻止其形成、稳定无活性的狭窄融合孔、改变融合孔扩张速度以及完全关闭融合孔来调节胞吐作用。融合孔的分子结构和动力学已成为细胞研究的主要焦点,尤其是作为治疗策略的一个有前景的靶点。电生理、光学和电化学方法已被广泛用于阐明细胞如何在单个融合孔水平上调节分泌。在此,我们描述了初始融合孔形成的结构和机制的最新进展以及治疗策略的进展,重点是胞吐作用。

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