Phosphatidylinositol 3-phosphate–binding protein AtPH1 controls the localization of the metal transporter NRAMP1

NRAMPs are transporters of iron (Fe) and manganese (Mn). The nramp3nramp4 double mutant arrests shortly after germination, due to its inability to remobilize Fe from seed vacuolar stores. Agorio et al. used a genetic approach to identify nns1, a partial suppressor of the growth-arrest phenotype. They mapped nns1 to AtPH1, a gene encoding a pleckstrin-homology (PH) domain protein. The PH domain binds the membrane lipid phosphatidylinositol 3-phosphate (PI3P) – PI3P and other phosphorylated PIs are known to specifically recruit proteins to membrane subdomains.  In the nns1 mutant that lacks AtPH1, NRAMP1 (normally found in the endosomal pathway and at the plasma membrane) is mislocalized to the vacuole, where it is thought to complement the missing iron transport function of the nramp3nramp4 mutant. Proc. Natl. Acad. Sci. USA 10.1073/pnas.1702975114