title: Iron transporter Nramp2/DMT-1 is associated with the membrane of phagosomes in macrophages and Sertoli cells.
abstract: Nramp2 (DMT1) is a pH-dependent divalent cation transporter that acts as the transferrin-independent iron uptake system at the intestinal brush border and also transports iron released from transferrin across the membrane of acidified endosomes. In this study, RAW264.7 macrophages and 2 independently derived murine Sertoli cells lines, TM4 and 15P-1, were used to further study the subcellular localization of Nramp2/DMT1 in phagocytic cells, including possible recruitment to the phagosomal membrane. Nramp2/DMT1 was localized primarily to the EEA1-positive recycling endosome compartment, with some overlapping staining with Lamp1-positive late endosomes. After phagocytosis, immunofluorescence analysis and in vitro biochemical studies using purified latex bead-containing phagosomes indicated Nramp2/DMT1 recruitment to the membrane of Lamp1, cathepsin D, and rab7-positive phagosomes. Nramp2/DMT1 was also found associated with erythrocyte-containing phagosomes in RAW macrophages and with the periphery of sperm-containing phagosomes in Sertoli cells. These results suggest that, as for the macrophage-specific Nramp1 protein, Nramp2/DMT1 may transport divalent metals from the phagosomal space.
authors.affiliation: Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
authors.forename: Nada
authors.initials: N
authors.lastname: Jabado
authors.forename: François
authors.initials: F
authors.lastname: Canonne-Hergaux
authors.forename: Samantha
authors.initials: S
authors.lastname: Gruenheid
authors.forename: Virgine
authors.initials: V
authors.lastname: Picard
authors.forename: Philippe
authors.initials: P
authors.lastname: Gros
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism*; D002458:Cell Fractionation; D002460:Cell Line; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D010587:Phagocytosis / Q000502:physiology*; D010588:Phagosomes / Q000378:metabolism*; D012708:Sertoli Cells / Q000378:metabolism*; D013094:Spermatozoa / Q000502:physiology; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D027682:Cation Transport Proteins; D033862:Iron-Binding Proteins; D000099236:Solute Carrier Family 11, Member 2