人类SLC1A5（ASCT2）氨基酸转运蛋白：从功能到结构以及在细胞生物学中的作用。,Frontiers in Cell and Developmental Biology

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人类SLC1A5（ASCT2）氨基酸转运蛋白：从功能到结构以及在细胞生物学中的作用。
Frontiers in Cell and Developmental Biology ( IF 4.6 ) Pub Date : 2018-09-21 , DOI: 10.3389/fcell.2018.00096
Mariafrancesca Scalise ₁ , Lorena Pochini ₁ , Lara Console ₁ , Maria A Losso ₁ , Cesare Indiveri _{1,

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Affiliation

SLC1A5（称为ASCT2）是属于SLC1家族的中性氨基酸转运蛋白，位于几个身体部位的质膜中。ASCT2是丙氨酸，丝氨酸，半胱氨酸转运蛋白2的首字母缩写，即使优选的底物是条件必需氨基酸谷氨酰胺，而半胱氨酸是调节剂而不是底物。关于细胞和组织中氨基酸转运的研究始于60年代，当时使用的是放射性标记化合物和竞争测定法。鉴定鼠类和人类基因后，已在细胞系统和蛋白脂质体中研究了编码蛋白的功能，发现该转运蛋白是依赖Na +的中性氨基酸逆转运蛋白，其中某些仅向内转运，而另一些则双向转运交换。功能不对称与动力学不对称合并在一起，符合氨基酸池协调的生理作用。已经描述了对于ASCT2的令人感兴趣的功能，其被一组逆转录病毒用作受体来感染人细胞。与支架蛋白的相互作用和翻译后修饰可调节ASCT2的稳定性，运输和运输活性。两个天冬酰胺残基，即N163和N212，是糖基化的位点，负责最终定位到质膜中。ASCT2在高度增殖的细胞（例如炎性细胞和干细胞）中表达增加，可以满足谷氨酰胺需求的增长。有趣的是，出于相同的原因，在许多人类癌症中，ASCT2的表达大大增强。这一发现引起了人们对其作为新抗癌药的药理学靶点的兴趣。最近解决的ASCT2的3D结构将有助于此类治疗化合物的合理设计。

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The Human SLC1A5 (ASCT2) Amino Acid Transporter: From Function to Structure and Role in Cell Biology.

SLC1A5, known as ASCT2, is a neutral amino acid transporter belonging to the SLC1 family and localized in the plasma membrane of several body districts. ASCT2 is an acronym standing for Alanine, Serine, Cysteine Transporter 2 even if the preferred substrate is the conditionally essential amino acid glutamine, with cysteine being a modulator and not a substrate. The studies around amino acid transport in cells and tissues began in the '60s by using radiolabeled compounds and competition assays. After identification of murine and human genes, the function of the coded protein has been studied in cell system and in proteoliposomes revealing that this transporter is a Na+ dependent antiporter of neutral amino acids, some of which are only inwardly transported and others are bi-directionally exchanged. The functional asymmetry merged with the kinetic asymmetry in line with the physiological role of amino acid pool harmonization. An intriguing function has been described for ASCT2 that is exploited as a receptor by a group of retroviruses to infect human cells. Interactions with scaffold proteins and post-translational modifications regulate ASCT2 stability, trafficking and transport activity. Two asparagine residues, namely N163 and N212, are the sites of glycosylation that is responsible for the definitive localization into the plasma membrane. ASCT2 expression increases in highly proliferative cells such as inflammatory and stem cells to fulfill the augmented glutamine demand. Interestingly, for the same reason, the expression of ASCT2 is greatly enhanced in many human cancers. This finding has generated interest in its candidacy as a pharmacological target for new anticancer drugs. The recently solved 3D structure of ASCT2 will aid in the rational design of such therapeutic compounds.

更新日期：2019-11-01

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