University of Cambridge  

 Genetics and Infection Laboratory 

              
   
Introduction

Slc11a1/SLC11A1 (formerly Nramp1/NRAMP1)

Genetic and functional characterization of murine and human Slc11a1/SCL11A1 (formerly Nramp1/NRAMP1)encoding the natural resistance associated macrophage protein has been a major focus of our research. The gene encodes a polytopic integral membrane protein with 10-12 membrane spanning domains. Confocal and EM-gold studies demonstrate that wildtype Slc11a1 localizes to late endosomes/lysosomes of macrophages. Using GFP-tagged proteins we have demonstrated using transient and stable transfection that the murine mutant protein that carries a Gly/Asp amino acid substitution at position 169 in putative transmembrane domain 4 is retained and degraded in the ER.

We are also tracking down the motifs in Slc11a1 and the two isoforms of the related protein Slc11a2 that act as localization signals to target them to late endosomal/lysosomal versus early endosomal compartments. We used the Xenopus oocyte expression system to demonstrate that Slc11a1 is a H+/Fe2+,Zn2+, Mn2+ antiporter. We are currently working to establish a functional yeast complementation assay so that we can use mutagenesis to gain a better understanding of the transport function of the molecule, and to determine the key amino acids that make Slc11a1 an antiporter while Slc11a2 is a symporter. The action of Slc11a1 as a divalent cation transporter influences antigen processing for presentation via class II, endosomal fusion, resistance to infection, response to vaccination, and susceptibility to rheumatoid and juvenile rheumatoid arthritis.



Group Leader
Jenefer Blackwell

Group Members
Jean-Francois Popoff
Projects:-
Genetic susceptibility
to infectious disease
Slc11a1/SLC11A1
studies
From genome
to vaccines for
leishmaniasis
People
Publications
Collaborators
 
 
 
 
 
Last updated on the 11th August 2004
Maintained by Richard Francis.