The iron transport protein NRAMP2 is an integral membrane glycoprotein that colocalizes with transferrin in recycling endosomes

Samantha Gruenheid, François Canonne-Hergaux, Susan Gauthier, David Hackam, Sergio Grinstein, Philippe Gros

Research output: Contribution to journalArticle

Abstract

The natural resistance associated macrophage protein (Nramp) gene family is composed of two members in mammals, Nramp1 and Nramp2. Nramp1 is expressed primarily in macrophages and mutations at this locus cause susceptibility to infectious diseases. Nramp2 has a much broader range of tissue expression and mutations at Nramp2 result in iron deficiency, indicating a role for Nramp2 in iron metabolism. To get further insight into the function and mechanism of action of Nramp proteins, we have generated isoform specific anti-Nramp1 and anti-Nramp2 antisera. Immunoblotting experiments indicate that Nramp2 is present in a number of cell types, including hemopoietic precursors, and is coexpressed with Nramp1 in primary macrophages and macrophage cell lines. Nramp2 is expressed as a 90-100-kD integral membrane protein extensively modified by glycosylation (>40% of molecular mass). Subcellular localization studies by immunofluorescence and confocal microscopy indicate distinct and nonoverlapping localization for Nramp1 and Nramp2. Nramp1 is expressed in the lysosomal compartment, whereas Nramp2 is not detectable in the lysosomes but is expressed primarily in recycling endosomes and also, to a lower extent, at the plasma membrane, colocalizing with transferrin. These findings suggest that Nramp2 plays a key role in the metabolism of transferrin-bound iron by transporting free Fe2+ across the endosomal membrane and into the cytoplasm.

Original languageEnglish (US)
Pages (from-to)831-841
Number of pages11
JournalJournal of Experimental Medicine
Volume189
Issue number5
DOIs
StatePublished - Mar 1 1999
Externally publishedYes

Fingerprint

Endosomes
Membrane Glycoproteins
Transferrin
Carrier Proteins
Iron
Macrophages
Mutation
Lysosomes
Glycosylation
Fluorescence Microscopy
Immunoblotting
Confocal Microscopy
Communicable Diseases
Immune Sera
Mammals
Protein Isoforms
Membrane Proteins
Cytoplasm
Cell Count
Cell Membrane

Keywords

  • Anemia
  • Infection
  • Iron
  • Macrophage
  • Transport

ASJC Scopus subject areas

  • Immunology

Cite this

The iron transport protein NRAMP2 is an integral membrane glycoprotein that colocalizes with transferrin in recycling endosomes. / Gruenheid, Samantha; Canonne-Hergaux, François; Gauthier, Susan; Hackam, David; Grinstein, Sergio; Gros, Philippe.

In: Journal of Experimental Medicine, Vol. 189, No. 5, 01.03.1999, p. 831-841.

Research output: Contribution to journalArticle

Gruenheid, Samantha ; Canonne-Hergaux, François ; Gauthier, Susan ; Hackam, David ; Grinstein, Sergio ; Gros, Philippe. / The iron transport protein NRAMP2 is an integral membrane glycoprotein that colocalizes with transferrin in recycling endosomes. In: Journal of Experimental Medicine. 1999 ; Vol. 189, No. 5. pp. 831-841.
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