The glutamine commute: Lost in the tube?

The glutamine commute: Lost in the tube?
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DOI:
10.1016/j.neuint.2005.11.016
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发表时间:
2006-05-01
影响因子:
4.2
通讯作者:
Melone, M
Melone, M
中科院分区:
医学3区
文献类型:
--
作者:
Conti, F;Melone, M

文献摘要

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“谷氨酸-谷氨酰胺”循环似乎在神经元和星形胶质细胞之间的谷氨酸(Glu)再循环中具有重要的(尽管不是唯一的)作用。最近的研究表明,谷氨酰胺(Gln)从星形胶质细胞的流出是由SNAT 3(以前的SN 1),定位于突触周围星形胶质细胞的N系统氨基酸转运蛋白介导的,而其流入神经元被认为是由系统A家族的转运蛋白,特别是SNAT 1和SNAT 2介导的。然而,我们的共聚焦和电子显微镜免疫细胞化学研究的结果显示,这些转运蛋白在大脑皮层的本地化,SNAT 1和SNAT 2的皮质神经元的体树突结构域中表达强劲,但很少轴突终端。为了排除固定和程序变量对轴突终末SNAT 1和SNAT 2免疫反应性检测的可能影响,我们使用了非常规免疫细胞化学方法,在某些情况下,提高了抗原检测。尽管这两种转运蛋白表达的轴突终末百分比略有增加。这些技术证明SNAT 1和SNAT 2确实很少定位于轴突末端。因此,我们的数据表明,SNAT 1和SNAT 2都不符合“谷氨酸-谷氨酰胺”循环中假定作用的标准,并表明其他Gln转运蛋白(孤儿或尚未鉴定)必须在轴突终末表达并维持Glu(和γ-氨基丁酸)神经递质库。(C)2006爱思唯尔有限公司保留所有权利。
The "glutamate-glutamine" cycle appears to have an important, albeit not exclusive role, in the recycling of glutamate (Glu) between neurons and astrocytes. Recent studies show that the efflux of glutamine (Gln) from astrocytes is mediated by SNAT3 (formerly SN1), a system N amino acid transporter localized to perisynaptic astrocytes, whereas its influx into neurons is thought to be mediated by transporters of the system A family, specifically SNAT1 and SNAT2. However, the results of our confocal and electron microscopy immunocytochemical studies of the localization of these transporters in the cerebral cortex show that SNAT1 and SNAT2 are robustly expressed in the somatodendritic domain of cortical neurons, but rarely to axon terminals. To rule out a possible influence of fixation and procedural variables on detection of SNAT1 and SNAT2 immunoreactivity in axon terminals, we used non-conventional immunocytochemical methods, which, in certain cases, improve antigen detection. Though evidencing a slightly increased percentage of axon terminals expressing the two transporters. these techniques demonstrated that SNAT1 and SNAT2 are indeed rarely localized to axon terminals. Our data thus suggest that neither SNAT1 nor SNAT2 meet the criteria for their postulated role in the "glutamate-glutamine" cycle, and indicate that other Gln transporters (either orphan or yet to be identified) must be expressed at axon terminals and sustain the Glu (and gamma-aminobutyric acid) neurotransmitter pool (s). (C) 2006 Elsevier Ltd. All rights reserved.