School of Pharmaceutical Sciences, Tsinghua University, Beijing, China.
Advanced Biotechnology and Application Research Center, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, China.
J Mol Cell Biol. 2019 Jan 1;11(1):1-13. doi: 10.1093/jmcb/mjy052.
The prevalence of metabolic diseases is growing worldwide. Accumulating evidence suggests that solute carrier (SLC) transporters contribute to the etiology of various metabolic diseases. Consistent with metabolic characteristics, the top five organs in which SLC transporters are highly expressed are the kidney, brain, liver, gut, and heart. We aim to understand the molecular mechanisms of important SLC transporter-mediated physiological processes and their potentials as drug targets. SLC transporters serve as 'metabolic gate' of cells and mediate the transport of a wide range of essential nutrients and metabolites such as glucose, amino acids, vitamins, neurotransmitters, and inorganic/metal ions. Gene-modified animal models have demonstrated that SLC transporters participate in many important physiological functions including nutrient supply, metabolic transformation, energy homeostasis, tissue development, oxidative stress, host defense, and neurological regulation. Furthermore, the human genomic studies have identified that SLC transporters are susceptible or causative genes in various diseases like cancer, metabolic disease, cardiovascular disease, immunological disorders, and neurological dysfunction. Importantly, a number of SLC transporters have been successfully targeted for drug developments. This review will focus on the current understanding of SLCs in regulating physiology, nutrient sensing and uptake, and risk of diseases.
代谢性疾病在全球范围内的患病率正在不断上升。越来越多的证据表明，溶质载体（SLC）转运蛋白与各种代谢性疾病的病因有关。与代谢特征一致，SLC 转运蛋白高度表达的前五个器官是肾脏、大脑、肝脏、肠道和心脏。我们旨在了解重要 SLC 转运蛋白介导的生理过程的分子机制及其作为药物靶点的潜力。SLC 转运蛋白是细胞的“代谢门”，可介导多种必需营养物质和代谢物的运输，如葡萄糖、氨基酸、维生素、神经递质和无机/金属离子。基因修饰动物模型表明，SLC 转运蛋白参与许多重要的生理功能，包括营养供应、代谢转化、能量平衡、组织发育、氧化应激、宿主防御和神经调节。此外，人类基因组研究表明，SLC 转运蛋白是癌症、代谢性疾病、心血管疾病、免疫性疾病和神经功能障碍等多种疾病的易感或致病基因。重要的是，一些 SLC 转运蛋白已成功成为药物开发的靶点。这篇综述将重点介绍 SLC 在调节生理、营养感应和摄取以及疾病风险方面的最新研究进展。
