Understanding the multiple functions of Nramp1

Microbes Infect. 2000 Mar;2(3):317-21. doi: 10.1016/s1286-4579(00)00295-1.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cation Transport Proteins*
  • Communicable Diseases / metabolism
  • Disease Susceptibility / metabolism
  • Humans
  • Ion Transport
  • Macrophages / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Metals / metabolism
  • Polymorphism, Genetic
  • Promoter Regions, Genetic


  • Carrier Proteins
  • Cation Transport Proteins
  • Membrane Proteins
  • Metals
  • natural resistance-associated macrophage protein 1