Abstract
AQP9 is an aquaglyceroporin with a very broad substrate spectrum. In addition to its orthodox nutrient substrates, AQP9 also transports multiple neutral and ionic arsenic species including arsenic trioxide, monomethylarsenous acid (MAsIII) and dimethylarsenic acid (DMAV). Here we discovered a new group of AQP9 substrates which includes two clinical relevant selenium species. We showed that AQP9 efficiently transports monomethylselenic acid (MSeA) with a preference for acidic pH, which has been demonstrated in Xenopus laevis oocyte following the overexpression of human AQP9. Specific inhibitors that dissipate transmembrane proton potential or change the transmembrane pH gradient, such as FCCP, valinomycin and nigericin did not significantly inhibit MSeA uptake, suggesting MSeA transport is not proton coupled. AQP9 was also found to transport ionic selenite and lactate, with much less efficiency compared with MSeA uptake. Selenite and lactate uptake via AQP9 is pH dependent and inhibited by FCCP and nigericin, but not valinomycin. The selenite and lactate uptake via AQP9 can be inhibited by different lactate analogs, indicating that their translocation share similar mechanisms. AQP9 transport of MSeA, selenite and lactate is all inhibited by a previously identified AQP9 inhibitor, phloretin, and the AQP9 substrate arsenite (AsIII). These newly identified AQP9 selenium substrates imply that AQP9 play a significant role in MSeA uptake and possibly selenite uptake involved in cancer therapy under specific microenvironments.
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This work was supported by NIH ES022800 to Z.L.
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Geng, X., McDermott, J., Lundgren, J. et al. Role of AQP9 in transport of monomethyselenic acid and selenite. Biometals 30, 747–755 (2017). https://doi.org/10.1007/s10534-017-0042-x
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DOI: https://doi.org/10.1007/s10534-017-0042-x