Resolving the biological role of the Rhesus (Rh) proteins of red blood cells with the aid of a green alga

The presence or absence of Rh antigens, abundant components of the red blood cell (RBC) plasma membrane, is a major cause of blood transfusion incompatibility and of hemolytic disease of the newborn. As deduced from studies on Rh_null erythrocytes, the Rh complex of RBC includes the Rh-associated glycoprotein RhAG, the Rh polypeptides, CD47, LW proteins, and glycophorin B (1). RhAG is essential for the assembly of the Rh complex, and mutations in RhAG result in the Rh_null syndrome (2). Despite their significance and intensive research, the biological role of the Rh protein complex remains controversial. This controversy may be accounted for by the fact that RhAG homologues are found in other mammalian tissues and in many lower organisms (3), including unicellular eukaryotes (4). Studies by Marini and colleagues (3) identified some homology (20–27% identity) between RhAG and Mep/Amt ammonium and methylammonium transporters in various organisms and suggested that the erythroid RhAG may function as an ammonium transporter (3). This finding was supported by the observation that RhAG (and its kidney-located homologue) could complement a yeast mutant impaired in ammonium uptake. Further, RhAG enhanced efflux of a preloaded methylammonium from yeast, suggesting that it might be involved in ammonium export as well (5). The notion that RhAG and its homologues are involved in transfer gained additional support by the observation that expression of RhCG, a mammalian nonerythroid homologue of RhAG, along the rat nephron, matched that expected from ammonium excretion activities of the respective nephron sections (6). An exciting …