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The SLC transporter in nutrient and metabolic sensing, regulation, and drug development
Yong Zhang 1,2,† , Yuping Zhang 1,† , Kun Sun 1 , Ziyi Meng 1 , and Ligong Chen 1,*
1 School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China
2 Advanced Biotechnology and Application Research Center, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100024, China
These authors contributed equally to this work.
*Correspondence to:Ligong Chen, E-mail: ligongchen@biomed.tsinghua.edu.cn
J Mol Cell Biol, Volume 11, Issue 1, January 2019, Pages 1-13  https://doi.org/10.1093/jmcb/mjy052
Keyword: SLC transporters, disease loci, nutrient and metabolic sensing, drug development
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.