Plants directly assimilate minerals from the environment and thus are key for acquisition of metals by all subsequent consumers. Limited bio-availability of copper, zinc and iron in soil decreases both the agronomic productivity and the nutrient quality of crops. Understanding the molecular mechanisms underlying metal homeostasis in plants is a prerequisite to optimizing plant yield and metal nutrient content. To absorb and maintain a balance of potentially toxic metal ions, plants utilize poorly understood mechanisms involving a large number of membrane transporters and metalbinding proteins with overlapping substrate specificities and complex regulation. To better understand the function and the integrated regulation, we analyzed in Arabidopsis the expression patterns in roots and in leaves of 53 genes coding for known or potential metal transporters, in response to copper, zinc, and iron deficiencies in Arabidopsis. Comparative analysis of gene expression profiles revealed specific transcriptional regulation by metals of the genes contrasting with the known wide substrate specificities of the encoded transporters. Our analysis suggested novel transport roles for several gene products and we used functional complementation of yeast mutants to correlate specific regulation by metals with transport activity. We demonstrate that two ZIP genes, ZIP2 and ZIP4, are involved in copper transport. We also present evidence that AtOPT3, a member of the oligopeptide transporter gene family with significant similarities to the maize iron-phytosiderophore transporter YS1, is regulated by metals and heterologous expression AtOPT3 can rescue yeast mutants deficient in metal transport.All organisms require metal prosthetic groups for their unique catalytic and structural properties. In proteins, copper and iron catalyze reduction-oxidation reactions, while zinc plays an essential structural or enzymatic role. Yet most metal ions are very reactive and can be toxic to cells when present in excess. Thus, it is important for organisms to maintain adequate levels of metals in tight homeostasis using complex and often evolutionarily conserved mechanisms for the uptake and transport of low solubility metals and storage of metal ions in a non-toxic form. Despite rapid progress in recent years of our understanding of metal homeostasis in yeast, (1) our knowledge of metal metabolism in plants is still rudimentary (2).A large number of cation transporters potentially involved in metal ion homeostasis have been identified on the genome of the model plant Arabidopsis thaliana (3). Several members of the 15 ZIP gene family (4) and of the 6 NRAMP family of transporters (3) have been characterized and shown to be involved in metal uptake and transport in plants (5-10). ABC transporters (11) and P-type ATPase pumps (12, 13) are also known to be involved in metal ions trafficking metals into organelles. Since metals are cytotoxic as free ions, they are chelated for both intracellular storage and long-distance transport. These chelators are eith...