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Putative role of the H+/sucrose symporter SLC45A3 as an osmolyte transporter in the kidney

  • Ion channels, receptors and transporters
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Abstract

The solute carrier family 45 a3 member (SLC45A3), known also as prostein, has been implicated with prostate cancer and the regulation of lipid metabolism in oligodendrocytes. Recently, we expressed SLC45A3 in yeast cells and characterised it as a proton-coupled sucrose symporter. However, the physiological functions of SLC45A3 were still unknown. Here, we report that SLC45A3 occurs in the kidney and is highly expressed in the medullary collecting duct (IMCD), a part of the kidney responsible for final urine concentration and faced to hyperosmotic environment. Moreover, messenger RNA (mRNA) expression of endogenous SLC45A3 in rat IMCD cells as well as in NRK52E cells increased up to four-fold under hyperosmotic conditions at 600 mOsmol/kg. Using NRK52E cells as an experimental model, we investigated the proton-coupled sugar transport and found that the uptake of sucrose or glucose was enhanced by hyperosmolarity. Down-regulation of expression by small interfering RNA (siRNA) decreased the osmotically inducible part of sucrose uptake and confirmed the involvement of SLC45A3 in this process. Furthermore, we observed an up to four-fold elevation of sucrose uptake triggered by hyperosmolarity across the apical membrane of NRK52E cells, while uptake across the basolateral membrane was not affected. Due to this finding, we conclude that SLC45A3 may occur at the luminal side of kidney epithelial cells and thus may take up solutes from the tubular fluid. Altogether, we show that SLC45A3 is a novel sugar transporter in kidney and hypothesise that the disaccharide sucrose, and probably the monosaccharides glucose and fructose, may serve as compatible osmolytes in urine.

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Acknowledgements

We thank Margret Düvel and Sabine Heuer for excellent technical assistance. Thanks also to Prof. Birgitta Burckhardt and Prof. Gerhard Burckhardt for many helpful discussions and for reading of the manuscript.

This work was supported by the Deutsche Forschungsgemeinschaft (VI 673/2-1, WI 698/7-1) and by the “Incentive Award of the Faculty of Biology/Chemistry” of the University of Osnabrück.

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Authors and Affiliations

  1. Department of Biology/Chemistry, Division of Animal Physiology, University of Osnabrück, Osnabrück, Germany

    Olga Vitavska & Helmut Wieczorek

  2. Department of Medicine, Hematology and Oncology, University of Halle, Halle, Germany

    Bayram Edemir

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  1. Olga Vitavska
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  2. Bayram Edemir
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  3. Helmut Wieczorek
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Correspondence to Olga Vitavska.

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Vitavska, O., Edemir, B. & Wieczorek, H. Putative role of the H+/sucrose symporter SLC45A3 as an osmolyte transporter in the kidney. Pflugers Arch - Eur J Physiol 468, 1353–1362 (2016). https://doi.org/10.1007/s00424-016-1841-6

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  • DOI: https://doi.org/10.1007/s00424-016-1841-6

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