Sodium-coupled neurotransmitter transporters play a fundamental role in the termination of synaptic neurotransmission, which makes them a major drug target. The reconstitution of these secondary active transporters into liposomes has shed light on their molecular transport mechanisms. From the earliest days of the reconstitution technique up to today's single-molecule studies, insights from live functioning transporters have been indispensable for our understanding of their physiological impact. The two classes of sodium-coupled neurotransmitter transporters, the neurotransmitter: sodium symporters and the excitatory amino acid transporters, have vastly different molecular structures, but complementary proteoliposome studies have sought to unravel their ion-dependence and transport kinetics. Furthermore, reconstitution experiments have been used on both protein classes to investigate the role of e.g. the lipid environment, of posttranslational modifications, and of specific amino acid residues in transport. Techniques that allow the detection of transport at a single-vesicle resolution have been developed, and single-molecule studies have started to reveal single transporter kinetics, which will expand our understanding of how transport across the membrane is facilitated at protein level. Here, we review a selection of the results and applications where the reconstitution of the two classes of neurotransmitter transporters has been instrumental.

中文翻译：

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通过重构阐明钠偶联神经递质转运蛋白背后的机制。

钠偶联神经递质转运蛋白在突触神经传递的终止中发挥着重要作用，这使其成为主要的药物靶点。这些二级活性转运蛋白重组为脂质体揭示了它们的分子转运机制。从最早的重组技术到今天的单分子研究，来自活体功能转运蛋白的见解对于我们理解它们的生理影响是必不可少的。两类钠偶联神经递质转运蛋白，即神经递质：钠转运蛋白和兴奋性氨基酸转运蛋白，具有截然不同的分子结构，但互补的蛋白脂质体研究试图揭示它们的离子依赖性和转运动力学。此外，重组实验已用于两种蛋白质类别，以研究脂质环境、翻译后修饰和特定氨基酸残基在转运中的作用。已经开发了允许以单囊泡分辨率检测转运的技术，并且单分子研究已经开始揭示单转运蛋白动力学，这将扩大我们对如何在蛋白质水平促进跨膜转运的理解。在这里，我们回顾了两类神经递质转运蛋白的重组所发挥的作用的结果和应用的选择。已经开发了允许以单囊泡分辨率检测转运的技术，并且单分子研究已经开始揭示单转运蛋白动力学，这将扩大我们对如何在蛋白质水平促进跨膜转运的理解。在这里，我们回顾了两类神经递质转运蛋白的重组所发挥的作用的结果和应用的选择。已经开发了允许以单囊泡分辨率检测转运的技术，并且单分子研究已经开始揭示单转运蛋白动力学，这将扩大我们对如何在蛋白质水平促进跨膜转运的理解。在这里，我们回顾了两类神经递质转运蛋白的重组所发挥的作用的结果和应用的选择。