Structure and function of multidrug and toxin extrusion proteins (MATEs) and their relevance to drug therapy and personalized medicine

Abstract

Multidrug and toxin extrusion (MATE; SLC47A) proteins are membrane transporters mediating the excretion of organic cations and zwitterions into bile and urine and thereby contributing to the hepatic and renal elimination of many xenobiotics. Transported substrates include creatinine as endogenous substrate, the vitamin thiamine and a number of drug agents with in part chemically different structures such as the antidiabetic metformin, the antiviral agents acyclovir and ganciclovir as well as the antibiotics cephalexin and cephradine. This review summarizes current knowledge on the structural and molecular features of human MATE transporters including data on expression and localization in different tissues, important aspects on regulation and their functional role in drug transport. The role of genetic variation of MATE proteins for drug pharmacokinetics and drug response will be discussed with consequences for personalized medicine.

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Acknowledgments

This work was supported in part by the Robert-Bosch Foundation, Stuttgart, Germany, the ICEPHA Grant Tübingen-Stuttgart, Germany, and the UGPx EU H2020 Grant (#668353).

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Correspondence to Anne T. Nies.

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Nies, A.T., Damme, K., Kruck, S. et al. Structure and function of multidrug and toxin extrusion proteins (MATEs) and their relevance to drug therapy and personalized medicine. Arch Toxicol 90, 1555–1584 (2016). https://doi.org/10.1007/s00204-016-1728-5

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Keywords

  • Function
  • MATE
  • Metformin
  • Multidrug and toxin extrusion
  • Polymorphisms
  • SLC47