The SLC6 transporters: perspectives on structure, functions, regulation, and models for transporter dysfunction.
The SLC6 transporters: perspectives on structure, functions, regulation, and models for transporter dysfunction.
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DOI：
10.1007/s00424-013-1410-1
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发表时间：
2014-01
影响因子：
4.5
通讯作者：
Verrey, Francois
中科院分区：
文献类型：
--
作者：
Rudnick, Gary;Kraemer, Reinhard;Blakely, Randy D.;Murphy, Dennis L.;Verrey, Francois
关键词：
人类SLC6家族由大约20个结构上相关的共转运蛋白组成，它们利用跨膜电化学梯度将底物主动导入细胞。这些转运蛋白的底物大约有一半是氨基酸，其他转运蛋白则运输生物胺和/或密切相关的化合物，如营养素和相容的渗透调节物质。在这篇简短的综述中，该领域的五位领导者讨论了涉及SLC6转运蛋白的一些当前重要的研究主题，强调了它们在广泛的不同功能范围内所发挥的综合作用。加里·鲁德尼克的第一篇文章描述了它们耦合运输的分子机制，根据新的晶体结构、功能研究和建模，人们正在逐步更好地了解这一机制。接下来，Reinhard Krämer在相关细菌甜菜碱转运蛋白BetP的渗透调节和胁迫反应的背景下讨论了多水平转运蛋白调节的问题。François Verrey随后对人类SLC6家族中作为营养氨基酸转运体的特定成员的作用进行了综述。他讨论了其中一些转运蛋白如何调节肠道和肾小管上皮细胞主动摄取(必需)氨基酸，以支持全身氨基酸需求，而另一些转运蛋白则在特定细胞中表达，以支持其专门化的新陈代谢和/或生长。人类SLC6家族中研究最广泛的成员是神经递质再摄取转运体，其中许多是治疗神经精神疾病的重要药物靶点。兰迪·布莱克利讨论了这些蛋白质的转录后修饰在调节转运蛋白、亚细胞定位和活性状态中的作用。最后，丹尼斯·墨菲回顾了自然基因变体和小鼠遗传模型如何表现出与细胞外神经递质水平变化相关的一致的行为变化。
The human SLC6 family is composed of approximately 20 structurally related symporters (co-transporters) that use the transmembrane electrochemical gradient to actively import their substrates into cells. Approximately half of the substrates of these transporters are amino acids, with others transporting biogenic amines and/or closely related compounds, such as nutrients and compatible osmolytes. In this short review, five leaders in the field discuss a number of currently important research themes that involve SLC6 transporters, highlighting the integrative role they play across a wide spectrum of different functions. The first essay, by Gary Rudnick, describes the molecular mechanism of their coupled transport which is being progressively better understood based on new crystal structures, functional studies, and modeling. Next, the question of multiple levels of transporter regulation is discussed by Reinhard Krämer, in the context of osmoregulation and stress response by the related bacterial betaine transporter BetP. The role of selected members of the human SLC6 family that function as nutrient amino acid transporters is then reviewed by François Verrey. He discusses how some of these transporters mediate the active uptake of (essential) amino acids into epithelial cells of the gut and the kidney tubule to support systemic amino acid requirements, whereas others are expressed in specific cells to support their specialized metabolism and/or growth. The most extensively studied members of the human SLC6 family are neurotransmitter reuptake transporters, many of which are important drug targets for the treatment of neuropsychiatric disorders. Randy Blakely discusses the role of posttranscriptional modifications of these proteins in regulating transporter subcellular localization and activity state. Finally, Dennis Murphy reviews how natural gene variants and mouse genetic models display consistent behavioral alterations that relate to altered extracellular neurotransmitter levels.
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影响因子：
30.3
作者：
Dierking, Katja;Polanowska, Jolanta;Pujol, Nathalie
通讯作者：
Pujol, Nathalie
影响因子：
6.2
作者：
Campbell NG;Zhu CB;Lindler KM;Yaspan BL;Kistner-Griffin E;NIH ARRA Consortium;Hewlett WA;Tate CG;Blakely RD;Sutcliffe JS
通讯作者：
Sutcliffe JS
影响因子：
7.2
作者：
Blakely, Randy D.;Edwards, Robert H.
通讯作者：
Edwards, Robert H.
DOI：
10.1523/jneurosci.0048-12.2012
发表时间：
2012-06-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chang JC;Tomlinson ID;Warnement MR;Ustione A;Carneiro AM;Piston DW;Blakely RD;Rosenthal SJ
通讯作者：
Rosenthal SJ
DOI：
10.1073/pnas.0804659105
发表时间：
2008-07-29
影响因子：
11.1
作者：
Forrest, Lucy R.;Zhang, Yuan-Wei;Rudnick, Gary
通讯作者：
Rudnick, Gary