Cellier, Mathieu 
ORCID: https://orcid.org/0000-0002-6084-434X et Gros, Philippe
(1997).
The NRAMP1 gene: Resistance to intracellular infections and antimicrobial activity of phagocytes
[Le gene NRAMP1: Resistance aux infections intracellulaires et activite antimicrobienne des phagocytes]
M/S : médecine sciences
, vol. 13
, nº 4.
pp. 501-508.
Résumé
The murine gene Bcg/Lsh/Ity controls innate resistance to various intracellular parasites. Loss of function mutations at Bcg are characterized by unrestricted growth of intracellular parasites such as Mycobacterium tuberculosis within the macrophages. A positional cloning strategy led to the identification of the candidate gene Nramp1 (natural resistance associated macrophage protein 1) which encodes an integral membrane phosphoglycoprotein composed of 12 putative transmembrane segments (TM). A single point mutation G169D within TM4 prevents normal expression of the protein and determines a susceptible phenotype similar to the experimental Nramp1 gene knockout. Nramp1 belongs to an evolutionary conserved family of membrane proteins. In mammals, two parologous genes are known and distinguished by their sequence conservation, chromosomal localization and mRNA expression pattern. While Nramp2 is quasi-ubiquitously expressed, Nramp1 expression is restricted to professional phagocytes (granulocytes and macrophages). The murine macrophage Nramp1 protein is expressed intracellularly and is recruited to the phagosomal membrane in which reside various types of intracellular parasites which growth is under the control of Bcg/Nramp1 alleles. Homologous genes have been identified in birds, invertebrates, plants, fungus and bacteria and sequences analyses predict a consensus topological model reminiscent of ion transport/permeation pathways. The yeast Smf1 homolog is expressed at the plasma membrane and has been implicated in Mn2+ uptake. It is interesting to speculate that Nramp1 and homologs expressed by intracellular parasites may compete for the uptake of Mn2+ ions from the intraphagosomal space and gain a metabolic advantage crucial for the outcome of their interactions.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | - |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 07 juill. 2025 18:24 |
| Dernière modification: | 07 juill. 2025 18:24 |
| URI: | https://espace.inrs.ca/id/eprint/14475 |
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