Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18
Modulation of the neuronal glutamate transporter EAAC1 by the interacting protein GTRAP3-18
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DOI：
10.1038/35065084
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发表时间：
2001-03-01
期刊：
影响因子：
64.8
通讯作者：
Rothstein, JD
中科院分区：
文献类型：
--
作者：
Lin, CLG;Orlov, I;Rothstein, JD
兴奋性氨基酸载体1 （EAAC1）是一种高亲和力Na+依赖性l-谷氨酸/D， l-天冬氨酸细胞膜转运蛋白1。它在大脑和一些非神经组织中表达。在大脑中，EAAC1是主要的神经元谷氨酸转运蛋白（2,3）。它在细胞内呈极化分布，主要功能是在细胞外环境中运输谷氨酸（2-4）。在肾脏中，它参与肾脏酸性氨基酸的再吸收和氨基酸代谢（5-7）。在这里，我们描述了eaac1相关蛋白GTRAP3-18的鉴定和表征。与EAAC1一样，GTRAP3-18在许多组织中表达（8,9）。它定位于细胞膜和细胞质，特异地与EAAC1的羧基端胞内结构域相互作用。增加细胞中GTRAP3-18的表达可通过降低底物亲和力来降低eaac1介导的谷氨酸转运。视黄酸可上调GTRAP3-18的表达，导致eaac1介导的谷氨酸转运特异性减少。这些研究表明谷氨酸转运蛋白可以被有效调节，GTRAP可以调节归因于EAAC1的转运功能。GTRAP3-18可能在调节EAAC1的代谢功能中起重要作用。
Excitatory amino-acid carrier 1 (EAAC1) is a high-affinity Na+-dependent L-glutamate/D, L-aspartate cell-membrane transport protein 1. It is expressed in brain as well as several non-nervous tissues. In brain, EAAC1 is the primary neuronal glutamate transporter(2,3). It has a polarized distribution in cells and mainly functions perisynaptically to transport glutamate from the extracellular environment(2-4). In the kidney it is involved in renal acidic amino-acid re-absorption and amino-acid metabolism(5-7). Here we describe the identification and characterization of an EAAC1-associated protein, GTRAP3-18. Like EAAC1, GTRAP3-18 is expressed in numerous tissues(8,9). It localizes to the cell membrane and cytoplasm, and specifically interacts with carboxy-terminal intracellular domain of EAAC1. Increasing the expression of GTRAP3-18 in cells reduces EAAC1-mediated glutamate transport by lowering substrate affinity. The expression of GTRAP3-18 can be upregulated by retinoic acid, which results in a specific reduction of EAAC1-mediated glutamate transport. These studies show that glutamate transport proteins can be regulated potently and that GTRAP can modulate the transport functions ascribed to EAAC1. GTRAP3-18 may be important in regulating the metabolic function of EAAC1.