Functional assessment of Nramp-like metal transporters and manganese in Caenorhabditis elegans.
Nramp1 (natural resistance-associated macrophage protein-1) is a functionally conserved iron-manganese transporter in macrophages. Manganese (Mn), a superoxide scavenger, is required in trace amounts and functions as a cofactor for most antioxidants. Three Nramp homologs, smf-1, smf-2, and smf-3, have been identified thus far in the nematode Caenorhabditis elegans. A GFP promoter assay revealed largely intestinal expression of the smf genes from early embryonic through adult stages. In addition, smf deletion mutants showed increased sensitivity to excess Mn and mild sensitivity to EDTA. Interestingly, these smf deletion mutants demonstrated hypersensitivity to the pathogen Staphylococcus aureus, an effect that was rescued by Mn feeding or knockdown of the Golgi calcium/manganese ATPase, pmr-1, indicating that Mn uptake is essential for the innate immune system. This reversal of pathogen sensitivity by Mn feeding suggests a protective and therapeutic role of Mn in pathogen evasion systems. We propose that the C. elegans intestinal lumen may mimic the mammalian macrophage phagosome and thus could be a simple model for studying Mn-mediated innate immunity.
Department of Biotechnology, West Bengal University of Technology, Kolkata 700-064, India.
Jaya
J
Bandyopadhyay
Hyun-Ok
HO
Song
Byung-Jae
BJ
Park
Gunasekaran
G
Singaravelu
Ju Lee
JL
Sun
Joohong
J
Ahnn
Jeong Hoon
JH
Cho
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D004492:Edetic Acid / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D007113:Immunity, Innate; D007413:Intestinal Mucosa / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism*; D013211:Staphylococcus aureus; D000099173:Natural Resistance-associated Macrophage Protein 1
D029742:Caenorhabditis elegans Proteins; D000252:Calcium-Transporting ATPases; D027682:Cation Transport Proteins; D004492:Edetic Acid; D008345:Manganese; D000099173:Natural Resistance-associated Macrophage Protein 1; C499334:pmr-1 protein, C elegans