Nramp1 locus encodes a 65 kDa interferon-γ-inducible protein in murine macrophages
Open accessAbstract
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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Nramp1 is a phagolysosomal transporter with homology to Dmt1 (Nramp2).
“A phagolysosomal transporter with homology to Dmt1 (Nramp2) is Nramp1 [8, 20, 71, 75].”
From “Pumping iron”—how macrophages handle iron at the systemic, microenvironmental, and cellular levels (2017) · cites this paper as [8]
Slc11a1 influences the course of infection with S. Typhimurium and certain species of Mycobacterium and Leishmania.
“Slc11a1 (also known as Nramp1) has long been known to influence the course of infection with S. Typhimurium and certain species of Mycobacterium and Leishmania (Vidal et al., 1993; Atkinson et al., 1997; Blackwell et al., 2003).”
From Genetic and Dietary Iron Overload Differentially Affect the Course of Salmonella Typhimurium Infection (2017) · cites this paper as Atkinson et al., 1997
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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
- Publisher
- Portland Press Ltd.
- Published
- 1997-08-01
- Volume
- 325
- Issue
- 3
- Pages
- 779-786
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1218623
- 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
- bronze
- doi.org
- 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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