CLONING AND FUNCTIONAL EXPRESSION OF A UREA TRANSPORTER FROM HUMAN BONE-MARROW CELLS

A rapid passive urea transport has been previously described in the ma mmalian renal inner medullary collecting duct epithelial cells and in mammalian erythrocytes, Recently, a vasopressin-regulated urea trans p orter (UT2) has been cloned from a rabbit kidney medullary cDNA librar y (You, G., Smith, C. P., Kanai. Y., Lee, W. S., Stelzner, M., and Hed iger, M. A. (1993) Nature 365, 844-847), We now report the cloning and character ization of a complementary DNA (HUT11) encoding an urea tra nsporter isolated from a human bone marrow library, It encodes a 43,00 0-Da polypeptide of 391 amino acids that exhibited 63% sequence identi ty with the rabbit urea transporter and a similar membrane topology, H UT11 carries 2 putative glycosylation sites and 10 cysteines, of which only 7 are conserved at an equivalent position in UT2, HUT11 transcri pts have been identified in human erythroid and renal tissues, Express ion studies in Xenopus oocytes demonstrated that HUT11 mediates a faci litated urea transport that was inhibited, as described in mammalian e rythrocytes, by very low concentrations of phloretin, p-chloromercurib enzene sulfonate, and urea analogues, No unidirectional movements of c harged molecules, glycerol, or water were associated with HUT11 expres sion in oocytes, These findings suggest that HUT11 is most likely resp onsible for the facilitated urea transport in human red blood cells.