Cited by 136Iron Metabolism and DisordersTrace Elements in HealthHeavy Metal Exposure and Toxicity

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Understanding the multiple functions of Nramp1

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Blackwell, Jenefer M, Searle, Susan, Goswami, Tapasree, Miller, E.Nancy·2000·Microbes and Infection

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Abstract

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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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)
DOI: 10.1016/s1286-4579(00)00295-1
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 8706 d)
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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Understanding the multiple functions of Nramp1

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