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Need for speed: Super-resolving the dynamic nanoclustering of syntaxin-1 at exocytic fusion sites.
Neuropharmacology ( IF 4.6 ) Pub Date : 2019-02-28 , DOI: 10.1016/j.neuropharm.2019.02.036
Pranesh Padmanabhan 1 , Adekunle T Bademosi 1 , Ravikiran Kasula 1 , Elsa Lauwers 2 , Patrik Verstreken 2 , Frédéric A Meunier 1
Affiliation  

Communication between cells relies on regulated exocytosis, a multi-step process that involves the docking, priming and fusion of vesicles with the plasma membrane, culminating in the release of neurotransmitters and hormones. Key proteins and lipids involved in exocytosis are subjected to Brownian movement and constantly switch between distinct motion states which are governed by short-lived molecular interactions. Critical biochemical reactions between exocytic proteins that occur in the confinement of nanodomains underpin the precise sequence of priming steps which leads to the fusion of vesicles. The advent of super-resolution microscopy techniques has provided the means to visualize individual molecules on the plasma membrane with high spatiotemporal resolution in live cells. These techniques are revealing a highly dynamic nature of the nanoscale organization of the exocytic machinery. In this review, we focus on soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) syntaxin-1, which mediates vesicular fusion. Syntaxin-1 is highly mobile at the plasma membrane, and its inherent speed allows fast assembly and disassembly of syntaxin-1 nanoclusters which are associated with exocytosis. We reflect on recent studies which have revealed the mechanisms regulating syntaxin-1 nanoclustering on the plasma membrane and draw inferences on the effect of synaptic activity, phosphoinositides, N-ethylmaleimide-sensitive factor (NSF), α-soluble NSF attachment protein (α-SNAP) and SNARE complex assembly on the dynamic nanoscale organization of syntaxin-1. This article is part of the special issue entitled 'Mobility and trafficking of neuronal membrane proteins'.

中文翻译:

对速度的需求:超级解析胞外融合位点上的syntaxin-1的动态纳米簇。

细胞之间的通讯依赖于调控的胞吐作用,这是一个多步骤的过程,涉及囊泡与质膜的对接,引发和融合,最终导致神经递质和激素的释放。参与胞吐作用的关键蛋白质和脂质会经历布朗运动,并在不同的运动状态之间不断切换,这些运动状态由短时的分子相互作用控制。胞外蛋白之间发生的关键生化反应发生在纳米域的限制内,这是引发步骤的精确顺序的基础,这些步骤会导致囊泡融合。超分辨率显微镜技术的出现提供了一种以高时空分辨率在活细胞中可视化质膜上单个分子的方法。这些技术揭示了胞外机制的纳米级组织的高度动态性质。在这篇综述中,我们专注于介导水泡融合的可溶性N-乙基马来酰亚胺敏感因子附着受体(SNARE)syntaxin-1。Syntaxin-1在质膜上具有很高的移动性,其固有的速度允许快速组装和拆卸与胞吐作用相关的Syntaxin-1纳米簇。我们回顾了最近的研究,这些研究揭示了调节质膜上的syntaxin-1纳米簇的机制,并推断出突触活性,磷酸肌醇,N-乙基马来酰亚胺敏感因子(NSF),α-可溶性NSF附着蛋白(α- SNAP)和SNARE复杂程序集在syntaxin-1的动态纳米级组织上。本文是标题为“
更新日期:2020-03-16
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