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Understanding the multiple functions of Nramp1
Open accessAbstract
Nramp1 regulates macrophage activation in infectious and autoimmune diseases. Nramp2 controls anaemia. Both are divalent cation (Fe(2+), Zn(2+), and Mn(2+)) transporters; Nramp2 a symporter of H(+) and metal ions, Nramp1 a H(+)/divalent cation antiporter. This provides a model for metal ion homeostasis in macrophages. Nramp2, localised to early endosomes, delivers extracellularly acquired divalent cations into the cytosol. Nramp1, localised to late endosomes/lysosomes, delivers divalent cations from the cytosol to phagolysosomes. Here, Fe(2+) generates antimicrobial hydroxyl radicals via the Fenton reaction. Zn(2+) and Mn(2+) may also influence endosomal metalloprotease activity and phagolysosome fusion. The many cellular functions dependent on metal ions as cofactors may explain the multiple pleiotropic effects of Nramp1, and its complex roles in infectious and autoimmune disease.
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“Iron homeostasis and Lnc2 formation are also linked to the activity of natural resistance associated macrophage protein 1 (NRAMP1 or SLC11A1), conferring resistance to infections with intracellular pathogens, such as Leishmania, Salmonella, or Mycobacteria (219, 220).”
From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [220]
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Metadata
- Authors
- Blackwell, J. M., Searle, S., Goswami, T., & Miller, E. N.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Blackwell, Jenefer M
- ORCID
- Blackwell, Jenefer M
- Venue
- Microbes and Infection
- Publisher
- Elsevier BV
- Published
- 2000-03
- Volume
- 2
- Issue
- 3
- Pages
- 317-321
- ISSN
- 1286-4579 (ISSN-L)
- OpenAlex
- W2131167151
- Cited by
- 136
- References
- 52
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 1 · 2018: 5 · 2017: 5 · 2016: 7 · 2015: 3 · 2014: 3 · 2013: 5 · 2012: 2
- FWCI
- 2.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Microbes and Infection (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
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Keywords
- NRAMP1, DMT1, divalent cation transport, metal homeostasis, macrophage activation, phagolysosomes, Fenton reaction, iron, zinc, manganese, phagolysosome fusion, anemia, infectious diseases, autoimmune disease
- MeSH terms
- Natural Resistance-associated Macrophage Protein 1, Animals, Autoimmune Diseases, Carrier Proteins, Communicable Diseases, Disease Susceptibility, Humans, Macrophages, Membrane Proteins, Metals, Polymorphism, Genetic, Promoter Regions, Genetic, Ion Transport, Cation Transport Proteins
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