Molecular characterization of ROSIT, a renal osmotic stress-induced Na(+)-Cl(-)-organic solute cotransporter.


A gene family encoding many Na(+)- and Cl(-)-dependent organic solute cotransporters has recently been recognized. Among the cotransporters that have been characterized are those for neurotransmitters, amino acids, and organic osmolytes. Using polymerase chain reaction and mRNA derived from renal cortex, we isolated a new member of this gene family, ROSIT, a renal osmotic stress-induced transporter. The cDNA is 2,354 bp long with an open reading frame of 1,845 bp. The 615 deduced amino sequence shows ROSIT to be most clearly related to two orphan cDNAs of this family isolated from brain. Northern analysis showed the mRNA is normally expressed in renal cortex but not in brain, heart, colon, liver, stomach, or skeletal muscle. Moreover, hypernatremic rats displayed a marked increase in mRNA levels in renal cortex, renal outer medulla, and perhaps intestine. Heterologous expression of the cRNA in Xenopus laevis oocytes failed to reveal the function of this gene product when analyzed with isotope fluxes or electrophysiological measurements using a wide variety of organic solutes. Although its function remains unknown, ROSIT is likely to be involved in kidney reclamation of an organic osmolyte or osmolyte precursor required for adaptation to hypertonic stress.