MOLECULAR-CLONING OF THE CDNA FOR AN MDCK CELL NA+-DEPENDENT AND CL--DEPENDENT TAURINE TRANSPORTER THAT IS REGULATED BY HYPERTONICITY

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