Cited by 81Iron Metabolism and DisordersTrace Elements in HealthImmune Response and Inflammation

Nramp1 locus encodes a 65 kDa interferon-γ-inducible protein in murine macrophages

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ATKINSON, Peter G. P., BLACKWELL, Jenefer M., BARTON, C. Howard·1997·Biochemical Journal

Abstract

The murine Nramp1 (natural-resistance-associated macrophage protein) locus, formerly known as Ity/Lsh/Bcg, was isolated previously on the basis of chromosomal location, and as conferring natural resistance to infection against intracellular macrophage pathogens. The gene encodes a transporter molecule of unknown function. We have prepared polyclonal antisera against the C-terminal 35 amino acids of murine Nramp1. This serum is reactive towards a 65 kDa protein, expressed in murine macrophage cells from resistant or susceptible mice stimulated with interferon-γ and lipopolysaccharide, but not in non-macrophage cells. Evidence indicates that Nramp1 is localized in a subcellular membrane rather than at the cell surface. This evidence includes: the identification of conserved endocytic targeting motifs following inspection of human and murine Nramp sequences; the enrichment of Nramp1, following magnetic selection of phagolysosomal vesicles from activated macrophages that were allowed to phagocytose magnetic, IgG-coated beads; confocal microscopy. These studies place Nramp1 on a membrane in close proximity to obligate intracellular pathogens. A link between Nramp1 and divalent-cation transport is suggested by sequence similarity with yeast SMF1. Evidence showing modulation of Nramp1 protein levels by iron chelation provides a direct link with Nramp1 function and divalent-cation metabolism.

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  1. Cellier, M., Prive, G., Belouchi, A., Kwan, T., Rodrigues, V., Chia, V. and Gros, P. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 10089-10093
  2. Supek, F., Supekova, L., Nelson, H. and Nelson, N. (1996) Proc. Natl. Acad. Sci.

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Authors
ATKINSON, P. G. P., BLACKWELL, J. M., & BARTON, C. H.
Affiliations
  • University of Southampton (GB)
  • University of Cambridge (GB)
Venue
Biochemical Journal
Published
1997-08-01
Volume
325
Issue
3
Pages
779-786
ISSN
  • 0264-6021 (ISSN-L)
  • 1470-8728
OpenAlex
W1946587221
Cited by
81
References
38
Citations by year
2025: 2 · 2021: 1 · 2020: 1 · 2019: 1 · 2017: 4 · 2014: 1 · 2013: 3 · 2012: 1
FWCI
5.77
Type
journal article
Language
en
Open access
Locations
  • Biochemical Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Wellcome Trust
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
NRAMP1, NRAMP, macrophages, natural resistance to infection, intracellular pathogens, phagolysosomes, membrane localization, divalent cation transport, iron chelation, lipopolysaccharide stimulation
MeSH terms
Natural Resistance-associated Macrophage Protein 1, Amino Acid Sequence, Animals, Carrier Proteins, Humans, Immune Sera, Interferon-gamma, Iron Chelating Agents, Macrophages, Membrane Proteins, Molecular Sequence Data, Sequence Homology, Amino Acid, Microglia, Cation Transport Proteins, Mice

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