Chapter category: Signal Transduction
Mouse Natural Resistance Associated Macrophage Protein 1 (Nramp1): A Key Master Player in Host Innate Immunity Against Infections
The Nramp Family
Edited by: Mathieu Cellier and Philippe GrosISBN: 0-306-47841-2
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Chapter authors:
Nada Jabado, Steven Lam-Yuk-Tseung, John R. Forbes and Philippe Gros
Nramp1 is one of the few host resistance genes that have been well characterized at the molecular and functional level. This protein is an integral transmembrane protein expressed in the lysosomal compartment of phagocytic cells and is recruited to the phagosomal membrane where it affects pathogen replication. Nramp1 is part of a large gene family conserved through evolution that codes for divalent cation transporters. In this chapter, we will summarize studies carried out on this gene in the mouse model, and will review recent work on the protein and its mechanism of action at the membrane of phagosomes formed in phagocytes. We propose that Nramp1 is a pH-dependent divalent cation efflux pump at the phagosomal membrane. It affects microbial replication by modulating divalent cation content in the phagosomal space.
Additional chapters from this book:
Plant Metal Transporters with Homology to Proteins of the NRAMP Family
Sebastien Thomine and Julian I. Schroeder
Plants need metal transporters to fulfill many essential functions ranging from metal absorption to metal sequestration and storage. In some cases, plants also have to deal with toxic heavy metals s...
Genetic Susceptibility to Infectious Diseases Linked to NRAMP1 Gene in Farm Animals
Judith Caron, Danielle Malo, Christopher Schutta, Joe W. Templeton and L. Garry Adams
Comparative genomics is playing a pivotal role in the genetic dissection of complex traits such as infectious diseases resistance. Using mouse models of infection, natural resistance associated macr...
Manganese and Iron Transport by Prokaryotic Nramp Family Transporters
Krisztina M. Papp, David G. Kehres and Michael E. Maguire
Initially identified in the mouse, the Nramp class of transport proteins is present in the majority of Eukaryota and Bacteria thus far investigated. In contrast very few Archaea appear to possess Nr...
Mouse Natural Resistance Associated Macrophage Protein 1 (Nramp1): A Key Master Player in Host Innate Immunity Against Infections
Nada Jabado, Steven Lam-Yuk-Tseung, John R. Forbes and Philippe Gros
Nramp1 is one of the few host resistance genes that have been well characterized at the molecular and functional level. This protein is an integral transmembrane protein expressed in the lysosomal c...
Role of Nramp Family in Pro-Inflammatory Diseases
Jenefer M. Blackwell, Hui-Rong Jiang and Jacqueline K. White
Early observations on the multiple pleiotropic effects of murine Slc11a1 (formerly Nramp1) on macrophage activation and pro-inflammatory responses prompted us to look for human SLC11A1 association w...
The Role of Yeast Nramp Metal Transporters in Manganese and Iron Homeostasis
Edward Luk, Laran Jensen and Valeria Culotta
The bakers yeast S. cerevisiae expresses three distinct Nramp metal transporters, namely Smf1p, Smf2p and Smf3p. Smf1p and Smf2p primarily function in manganese homeostasis, however these transporte...
Molecular Evolutionary Analysis of Nramp Family
Etienne Richer, Pascal Courville and Mathieu FM Cellier
The natural resistance-associated macrophage protein (Nramp) belongs to a family of ion permeases highly conserved in eukaryotes that originated in prokaryotes. Three phylogenetic groups of homologs...
Role of Nramp2 (DMT1) in Iron Homeostasis
Nancy C. Andrews
Nramp2 (DMT1) plays several important roles in iron metabolism. Investigations of animals carrying mutations in the Nramp2 (DMT1) gene have shown that the protein is critically important for absorpt...
Regulation of Bacterial MntH Genes
John D. Helmann
Bacterial NRAMP-like transporters, generically referred to as MntH proteins, appear to function primarily as Mn(II) uptake systems induced under conditions of manganese limitation. Regulation of mnt...
Molecular Physiology of the H+-coupled Iron Transporter DMT1
Bryan Mackenzie • Matthias A. Hediger
The mammalian DMT1 is a widely-expressed divalent metal-ion transporter that is energized by the H+ electrochemical gradient. Among the broad range of transition metal ions accepted as substrates, F...
Metal-ion Transporters— From Yeast to Human Diseases
Adiel Cohen, Hannah Nelson and Nathan Nelson
Transition metal ions such as copper, iron, manganese and zinc serve as essential cofac tors for a variety of biological processes including cell energetics, gene regulation and control of free radi...
Role of the Nramp Orthologue, MntH, in the Virulence of Mycobacterium Tuberculosis
P. Domenech and S.T. Cole
Mycobacterium tuberculosis is the causative agent of tuberculosis. The natural habitat of this pathogen is the alveolar macrophage where it modulates the maturation of the phagosome, inhibiting the ...
Tissue Distribution and Subcellular Localization of Nramp Proteins
François Canonne-Hergaux and Philippe Gros
The NRAMP family regroups divalent metal transporters highly conserved throughout evolution. In mammals, these membrane carriers play key roles in resistance to intracellular pathogens and in iron h...
Pleiotropic Effects of Nramp (Bcg/Lsh/Ity) Gene Expression on Macrophage Functions
Luis F. Barrera and Martin Olivier
Expression of Nramp1 gene in phagocytes has been correlated with resistance toward infections, restricting growth of various intracellular microbes within the phagolysosome environment. This gene co...
The NRAMP Genes and Human Susceptibility to Common Diseases
Audrey Poon and Erwin Schurr
Results obtained in murine models have raised the hope that human NRAMP genes could be important determinants of susceptibility for common human diseases. There is good agreement among studies condu...
Cellular and Tissue Expression of Rat DMT1 / Nramp 2
Evan H. Morgan
Evidence that rat DMT1 functions as a membrane transporter of iron was established by expression cloning in Xenopus laevis oocytes and by investigations in the Belgrade rat in which iron metabol...
