NOVEL LOCALIZATION OF A NA+ H+ EXCHANGER IN A LATE ENDOSOMAL COMPARTMENT OF YEAST - IMPLICATIONS FOR VACUOLE BIOGENESIS/

Na+/H+ exchangers catalyze the electrically silent countertransport of Na+ and H+, controlling the transmembrane movement of salt, water, an d acid-base equivalents, and are therefore critical for Na+ tolerance, cell volume control, and pH regulation. In contrast to numerous well studied plasma membrane isoforms (NHE1-4), much less is known about in tracellular Na+/H+ exchangers, and thus far no vertebrate isoform has been shown to have an exclusively endosomal distribution. In this cont ext, me show that the yeast NHE homologue, Nhx1 (Nass, R., Cunningham, K. W., and Rao, R. (1997) J. Biol. Chem. 272, 26145-26152), localizes uniquely to prevacuolar compartments, equivalent to late endosomes of animal cells. In living yeast, we show that these compartments closel y abut the vacuolar membrane in a striking bipolar distribution, sugge sting that vacuole biogenesis occurs at distinct sites. Nhx1 is the fo unding member of a newly emergent cluster of exchanger homologues, fro m yeasts, worms, and humans that may share a common intracellular loca lization. By compartmentalizing Na+, intracellular exchangers play an important role in halotolerance; furthermore, we hypothesize that salt and water movement into vesicles may regulate vesicle volume and pH a nd thus contribute to vacuole biogenesis.