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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >The family of sodium-dependent glutamate transporters: a focus on the GLT-1/EAAT2 subtype.
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The family of sodium-dependent glutamate transporters: a focus on the GLT-1/EAAT2 subtype.

机译：钠依赖性谷氨酸转运蛋白家族：重点研究GLT-1 / EAAT2亚型。

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The acidic amino acids, glutamate and aspartate, are the predominant excitatory neurotransmitters in the mammalian CNS. Under many pathologic conditions, these excitatory amino acids (EAAs) accumulate in the extracellular fluid in CNS and the resultant excessive activation of EAA receptors contributes to brain injury through a process known as 'excitotoxicity'. Unlike many other neurotransmitters, there is no evidence for extracellular metabolism of EAAs, rather, they are cleared by Na+-dependent transport mechanisms. Therefore, this transport process is important for ensuring crisp synaptic signaling as well as limiting the excitotoxic potential of EAAs. With the cloning of five distinct EAA transporters, a variety of tools were developed to characterize individual transporter subtypes, including specific antibodies, expression systems, and probes to delete/knock-down expression of each subtype. These tools are beginning to provide fundamental information that has the potential to impact our understanding of EAA physiology and pathophysiology. For example, biophysical studies of the cloned transporters have led to the observation that some subtypes function as ligand-gated ion channels as well as transporters. With these reagents, it has also been possible to explore the relative contributions of each transporter to the clearance of extracellular EAAs and to begin to examine the regulation of specific transporter subtypes. In this review, an overview of the properties of the transporter subtypes will be presented. The evidence which suggests that the transporter, GLT1/EAAT2, may be sufficient to explain a large percentage of forebrain transport will be critically reviewed. Finally, the studies of regulation of GLT-1 in vitro and in vivo will be described.
机译：酸性氨基酸谷氨酸和天冬氨酸是哺乳动物中枢神经系统中主要的兴奋性神经递质。在许多病理条件下，这些兴奋性氨基酸（EAA）积聚在CNS的细胞外液中，导致的EAA受体过度活化通过称为“兴奋性毒性”的过程而导致脑损伤。与许多其他神经递质不同，没有证据表明EAA会在细胞外代谢，而是通过Na +依赖性转运机制清除。因此，该运输过程对于确保突触信号的传导以及限制EAA的兴奋毒性潜力非常重要。通过克隆五个不同的EAA转运蛋白，开发了多种工具来表征单个转运蛋白亚型，包括特异性抗体，表达系统和删除/敲低每种亚型表达的探针。这些工具开始提供可能影响我们对EAA生理学和病理生理学理解的基础信息。例如，对克隆的转运蛋白的生物物理研究已导致观察到某些亚型可作为配体门控离子通道以及转运蛋白。使用这些试剂，还可能探索每种转运蛋白对清除细胞外EAA的相对贡献，并开始研究特定转运蛋白亚型的调节。在这篇综述中，将概述转运子亚型的性质。证据表明，转运蛋白GLT1 / EAAT2可能足以解释大部分前脑转运，将对此进行严格审查。最后，将描述体外和体内调节GLT-1的研究。

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