THE MACROPHAGE-SPECIFIC MEMBRANE-PROTEIN NRAMP CONTROLLING NATURAL-RESISTANCE TO INFECTIONS IN MICE HAS HOMOLOGS EXPRESSED IN THE ROOT-SYSTEM OF PLANTS

In mice, natural resistance or susceptibility to infection with Mycoba cteria, Salmonella, and Leishmania is controlled by a gene named Beg. Beg regulates the capacity of macrophages to limit intracellular repli cation of the ingested parasites, and is believed to regulate a key ba ctericidal mechanism of this cell. Recently, we have cloned the Beg ge ne and shown that it encodes a novel macrophage-specific membrane prot ein designated Nramp. A routine search of the public databases for seq uences homologous to Nramp identified 3 expressed sequence tags (EST) that show strong similarities to the mammalian protein. We report the identification and cloning of a full-length cDNA clone corresponding t o a plant homologue (OsNramp1) of mammalian Nramp. Predicted amino aci d sequence analysis of the plant protein indicates a remarkable degree of similarity (60% homology) with its mammalian counterpart, includin g identical number, position, and composition of transmembrane domains , glycosylation signals, and consensus transport motif, suggesting an identical overall secondary structure and membrane organization for th e two proteins. This high degree of structural similarity indicates th at the two proteins may be functionally related, possibly through a co mmon mechanism of transport. RNA hybridization studies and RT-PCR anal yses indicate that OsNramp1 mRNA is expressed primarily in roots and o nly at very low levels in leaves/stem. DNA hybridization studies indic ate that OsNramp1 is not a single gene, but rather forms part of a nov el gene family which has several members in all plants tested includin g cereals such as rice, wheat, and corn, and also in common weed speci es. The striking degree of conservation between the macrophage-specifi c mammalian Nramp and its OsNramp1 plant homologue is discussed with r espect to possible implications in the metabolism of nitrate in both o rganisms.