Glutamine transporters in mammalian cells and their functions in physiology and cancer.
Glutamine transporters in mammalian cells and their functions in physiology and cancer.
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DOI：
10.1016/j.bbamcr.2015.12.017
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发表时间：
2016-10
期刊：
影响因子：
--
通讯作者：
Ganapathy V
中科院分区：
文献类型：
--
作者：
Bhutia YD;Ganapathy V
哺乳动物细胞中的SLC（溶质载体）型转运蛋白（数量约为400）由52个不同的基因家族组成，仅基于转运蛋白的氨基酸序列（一级结构）而不是其转运功能进行分组。其中包括氨基酸的转运蛋白。其中14种能够跨质膜转运谷氨酰胺，分布在4个家族：SLC1、SLC6、SLC7和SLC38。然而，通常认为SLC 38家族的成员是谷氨酰胺的主要转运蛋白。一些谷氨酰胺转运蛋白是强制性的交换剂，而一些则在一个方向上起主动转运蛋白的作用。虽然大多数谷氨酰胺转运蛋白介导氨基酸流入细胞，但有些实际上介导氨基酸流出细胞。谷氨酰胺转运蛋白在多种组织中发挥重要作用，包括肝、脑、肾和胎盘，这从小鼠中特异性谷氨酰胺转运蛋白缺失导致的生物学和生化表型中清楚地证明。由于谷氨酰胺在肿瘤细胞生长和增殖中的重要作用，谷氨酰胺转运蛋白作为肿瘤治疗的潜在药物靶点在肿瘤生物学中受到越来越多的关注。某些谷氨酰胺转运蛋白的选择性阻断剂可能有效地阻止谷氨酰胺和其他重要氨基酸进入肿瘤细胞，从而基本上使这些细胞饿死。这可能代表着发现具有以前未探索的作用模式的新型抗癌药物的新时代的开始。
The SLC (solute carrier)-type transporters (∼400 in number) in mammalian cells consist of 52 distinct gene families, grouped solely based on the amino acid sequence (primary structure) of the transporter proteins and not on their transport function. Among them are the transporters for amino acids. Fourteen of them, capable of transporting glutamine across the plasma membrane, are found in four families: SLC1, SLC6, SLC7, and SLC38. However, it is generally thought that the members of the SLC38 family are the principal transporters for glutamine. Some of the glutamine transporters are obligatory exchangers whereas some function as active transporters in one direction. While most glutamine transporters mediate the influx of the amino acid into cells, some actually mediate the efflux of the amino acid out of the cells. Glutamine transporters play important roles in a variety of tissues, including the liver, brain, kidney, and placenta, as clearly evident from the biological and biochemical phenotypes resulting from the deletion of specific glutamine transporters in mice. Owing to the obligatory role of glutamine in growth and proliferation of tumor cells, there is increasing attention on glutamine transporters in cancer biology as potential drug targets for cancer treatment. Selective blockers of certain glutamine transporters might be effective in preventing the entry of glutamine and other important amino acids into tumor cells, thus essentially starving these cells to death. This could represent the beginning of a new era in the discovery of novel anticancer drugs with a previously unexplored mode of action.