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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Sep 1;89(17):8230–8234. doi: 10.1073/pnas.89.17.8230

Molecular cloning of the cDNA for an MDCK cell Na(+)- and Cl(-)-dependent taurine transporter that is regulated by hypertonicity.

S Uchida 1, H M Kwon 1, A Yamauchi 1, A S Preston 1, F Marumo 1, J S Handler 1
PMCID: PMC49891  PMID: 1518851

Abstract

Cells in the hypertonic renal medulla maintain their intracellular ion concentration at isotonic levels, despite much higher concentrations of extracellular electrolytes, by accumulating high concentrations of nonperturbing small organic solutes termed osmolytes. Taurine has been identified as a nonperturbing osmolyte in the renal medulla and Madin-Darby canine kidney (MDCK) cells. In hypertonic medium, the increased accumulation of taurine in MDCK cells is the result of increased activity of a Na(+)- and Cl(-)-dependent taurine transporter. We have isolated a cDNA encoding a Na(+)- and Cl(-)-dependent taurine transporter, whose sequence corresponds to a protein of 655 amino acids with significant amino acid sequence similarity to previously cloned Na(+)- and Cl(-)-dependent transporters, including the MDCK cell betaine/gamma-aminobutyric acid transporter and several brain neurotransmitter transporters. Northern hybridization indicates that mRNA for the taurine transporter is present in renal cortex and medulla, ileal mucosa, brain, liver, and heart. The abundance of mRNA for the taurine transporter is increased in MDCK cells cultured in hypertonic medium, suggesting that regulation of transport activity by medium hypertonicity occurs at the level of mRNA accumulation.

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Selected References

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  1. Barnard J. A., Thaxter S., Kikuchi K., Ghishan F. K. Taurine transport by rat intestine. Am J Physiol. 1988 Mar;254(3 Pt 1):G334–G338. doi: 10.1152/ajpgi.1988.254.3.G334. [DOI] [PubMed] [Google Scholar]
  2. Blakely R. D., Berson H. E., Fremeau R. T., Jr, Caron M. G., Peek M. M., Prince H. K., Bradley C. C. Cloning and expression of a functional serotonin transporter from rat brain. Nature. 1991 Nov 7;354(6348):66–70. doi: 10.1038/354066a0. [DOI] [PubMed] [Google Scholar]
  3. Bucuvalas J. C., Goodrich A. L., Suchy F. J. Hepatic taurine transport: a Na+-dependent carrier on the basolateral plasma membrane. Am J Physiol. 1987 Sep;253(3 Pt 1):G351–G358. doi: 10.1152/ajpgi.1987.253.3.G351. [DOI] [PubMed] [Google Scholar]
  4. Chesney R. W., Gusowski N., Dabbagh S. Renal cortex taurine content regulates renal adaptive response to altered dietary intake of sulfur amino acids. J Clin Invest. 1985 Dec;76(6):2213–2221. doi: 10.1172/JCI112230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chesney R. W. Taurine: its biological role and clinical implications. Adv Pediatr. 1985;32:1–42. [PubMed] [Google Scholar]
  6. Guastella J., Nelson N., Nelson H., Czyzyk L., Keynan S., Miedel M. C., Davidson N., Lester H. A., Kanner B. I. Cloning and expression of a rat brain GABA transporter. Science. 1990 Sep 14;249(4974):1303–1306. doi: 10.1126/science.1975955. [DOI] [PubMed] [Google Scholar]
  7. Hoffman B. J., Mezey E., Brownstein M. J. Cloning of a serotonin transporter affected by antidepressants. Science. 1991 Oct 25;254(5031):579–580. doi: 10.1126/science.1948036. [DOI] [PubMed] [Google Scholar]
  8. Jones D. P., Miller L. A., Chesney R. W. Adaptive regulation of taurine transport in two continuous renal epithelial cell lines. Kidney Int. 1990 Aug;38(2):219–226. doi: 10.1038/ki.1990.189. [DOI] [PubMed] [Google Scholar]
  9. Jones D. P., Miller L. A., Dowling C., Chesney R. W. Regulation of taurine transporter activity in LLC-PK1 cells: role of protein synthesis and protein kinase C activation. J Am Soc Nephrol. 1991 Nov;2(5):1021–1029. doi: 10.1681/ASN.V251021. [DOI] [PubMed] [Google Scholar]
  10. Kennelly P. J., Krebs E. G. Consensus sequences as substrate specificity determinants for protein kinases and protein phosphatases. J Biol Chem. 1991 Aug 25;266(24):15555–15558. [PubMed] [Google Scholar]
  11. Kilty J. E., Lorang D., Amara S. G. Cloning and expression of a cocaine-sensitive rat dopamine transporter. Science. 1991 Oct 25;254(5031):578–579. doi: 10.1126/science.1948035. [DOI] [PubMed] [Google Scholar]
  12. Kornfeld R., Kornfeld S. Assembly of asparagine-linked oligosaccharides. Annu Rev Biochem. 1985;54:631–664. doi: 10.1146/annurev.bi.54.070185.003215. [DOI] [PubMed] [Google Scholar]
  13. Kulanthaivel P., Cool D. R., Ramamoorthy S., Mahesh V. B., Leibach F. H., Ganapathy V. Transport of taurine and its regulation by protein kinase C in the JAR human placental choriocarcinoma cell line. Biochem J. 1991 Jul 1;277(Pt 1):53–58. doi: 10.1042/bj2770053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kwon H. M., Yamauchi A., Uchida S., Preston A. S., Garcia-Perez A., Burg M. B., Handler J. S. Cloning of the cDNa for a Na+/myo-inositol cotransporter, a hypertonicity stress protein. J Biol Chem. 1992 Mar 25;267(9):6297–6301. [PubMed] [Google Scholar]
  15. Kyte J., Doolittle R. F. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. doi: 10.1016/0022-2836(82)90515-0. [DOI] [PubMed] [Google Scholar]
  16. Meiners B. A., Speth R. C., Bresolin N., Huxtable R. J., Yamamura H. I. Sodium-dependent, high-affinity taurine transport into rat brain synaptosomes. Fed Proc. 1980 Jul;39(9):2695–2700. [PubMed] [Google Scholar]
  17. Miyamoto Y., Tiruppathi C., Ganapathy V., Leibach F. H. Active transport of taurine in rabbit jejunal brush-border membrane vesicles. Am J Physiol. 1989 Jul;257(1 Pt 1):G65–G72. doi: 10.1152/ajpgi.1989.257.1.G65. [DOI] [PubMed] [Google Scholar]
  18. Nakanishi T., Uyama O., Sugita M. Osmotically regulated taurine content in rat renal inner medulla. Am J Physiol. 1991 Dec;261(6 Pt 2):F957–F962. doi: 10.1152/ajprenal.1991.261.6.F957. [DOI] [PubMed] [Google Scholar]
  19. Pacholczyk T., Blakely R. D., Amara S. G. Expression cloning of a cocaine- and antidepressant-sensitive human noradrenaline transporter. Nature. 1991 Mar 28;350(6316):350–354. doi: 10.1038/350350a0. [DOI] [PubMed] [Google Scholar]
  20. Shimada S., Kitayama S., Lin C. L., Patel A., Nanthakumar E., Gregor P., Kuhar M., Uhl G. Cloning and expression of a cocaine-sensitive dopamine transporter complementary DNA. Science. 1991 Oct 25;254(5031):576–578. doi: 10.1126/science.1948034. [DOI] [PubMed] [Google Scholar]
  21. Taub M., Chuman L., Saier M. H., Jr, Sato G. Growth of Madin-Darby canine kidney epithelial cell (MDCK) line in hormone-supplemented, serum-free medium. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3338–3342. doi: 10.1073/pnas.76.7.3338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Uchida S., Kwon H. M., Preston A. S., Handler J. S. Expression of Madin-Darby canine kidney cell Na(+)-and Cl(-)-dependent taurine transporter in Xenopus laevis oocytes. J Biol Chem. 1991 May 25;266(15):9605–9609. [PubMed] [Google Scholar]
  23. Uchida S., Nakanishi T., Kwon H. M., Preston A. S., Handler J. S. Taurine behaves as an osmolyte in Madin-Darby canine kidney cells. Protection by polarized, regulated transport of taurine. J Clin Invest. 1991 Aug;88(2):656–662. doi: 10.1172/JCI115350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Usdin T. B., Mezey E., Chen C., Brownstein M. J., Hoffman B. J. Cloning of the cocaine-sensitive bovine dopamine transporter. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11168–11171. doi: 10.1073/pnas.88.24.11168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Yamauchi A., Uchida S., Kwon H. M., Preston A. S., Robey R. B., Garcia-Perez A., Burg M. B., Handler J. S. Cloning of a Na(+)- and Cl(-)-dependent betaine transporter that is regulated by hypertonicity. J Biol Chem. 1992 Jan 5;267(1):649–652. [PubMed] [Google Scholar]
  26. Yancey P. H., Clark M. E., Hand S. C., Bowlus R. D., Somero G. N. Living with water stress: evolution of osmolyte systems. Science. 1982 Sep 24;217(4566):1214–1222. doi: 10.1126/science.7112124. [DOI] [PubMed] [Google Scholar]
  27. Zelikovic I., Stejskal-Lorenz E., Lohstroh P., Budreau A., Chesney R. W. Anion dependence of taurine transport by rat renal brush-border membrane vesicles. Am J Physiol. 1989 Apr;256(4 Pt 2):F646–F655. doi: 10.1152/ajprenal.1989.256.4.F646. [DOI] [PubMed] [Google Scholar]

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