Zinc transporters that regulate vacuolar zinc storage in Saccharomyces cerevisiae

All cells regulate their intracellular zinc levels. In yeast, zinc uptake i s mediated by Zrt1p and Zrt2p, which belong to the ZIP family of metal tran sporters, Under zinc limitation, ZRT1 and ZRT2 transcription is induced by the Zap1p transcriptional activator. We describe here a new component of zi nc homeostasis, vacuolar zinc storage, that is also regulated by Zap1p. Zin c-replete cells accumulate zinc in the vacuole via the Zrc1p and Cot1p tran sporters. Our results indicate that another zinc transporter, Zrt3p, mobili zes this stored zinc in zinc-limited cells. ZRT3 is a Zap1p-regulated gene whose transcription increases in low zinc. Zrt3p is also a member of the ZI P family and it localizes to the vacuolar membrane. The effects of ZRT3 mut ation and overexpression on cell growth, cellular zinc accumulation and int racellular labile zinc pools are all consistent with its proposed role. Fur thermore, we demonstrate that zrt3 mutants inefficiently mobilize stored zi nc to offset deficiency. Thus, our studies define a system of zinc influx a nd efflux transporters in the vacuole that play important roles in zinc hom eostasis.