Manganese (Mn), an essential micronutrient, acts as a cofactor involved in multiple biological processes including photosynthesis, lipid biosynthesis and oxidative stress in plants. Natural Resistance-Associated Macrophage Proteins (NRAMPs) comprise a family that is evolutionarily conserved from bacteria to human beings and acts as proton/metal symporters that are able to transport a broad range of metals, including Fe²⁺, Mn²⁺, Zn²⁺ and Cd²⁺. NRAMP1 is a root high-affinity transporter for Mn uptake in Arabidopsis. Mutation of NRAMP1 impairs root growth under Mn deficient conditions. To identify additional genes required for Mn uptake and transport, we carried out a forward genetic screen on an EMS-mutagenized population in the nramp1 background in Arabidopsis. Through the screening for mutants that are sensitive to low Mn, we identified a mutant showing Mn-dependent short root growth. Gene cloning led to the identification of the responsible gene NRAMP2 that could complement the defective root growth in the mutant under Mn deficiency. Our results reveal that under Mn deficient conditions, increased accumulation of H₂O₂ is partially responsible for the root growth inhibition and that NRAMP2 is a Mn transporter localized in the trans-Golgi network and is involved in remobilization of Mn in Golgi for root growth. Overexpression of NRAMP2 improved plant growth at Mn-deficient conditions.

Besides NRAMP1 and NRAMP2, we found that NRAMP6 is also required for sustaining root growth at low Mn conditions. Although NRAMP6 was expressed in roots at a low level, NRAMP6 plays an unequal redundant role with NRAMP1 to be involved in the regulation of root growth and Mn translocation from roots to shoots under Mn deficient conditions. Overexpression of NRAMP6 improves root growth at low Mn conditions. Crops such as wheat and barley are prone to experience Mn deficiency when they are grown on high pH and low water content soils that are prevalent in northern parts of Europe, USA and China. Therefore, our results suggest a way to improve crop growth under Mn deficient conditions through manipulation of NRAMP2 and NRAMP6.