Functional assessment of Nramp-like metal transporters and manganese in Caenorhabditis elegans.

Abstract

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.

• Authors: Jaya Bandyopadhyay, Hyun-Ok Song, Byung-Jae Park, Gunasekaran Singaravelu, Ju Lee Sun, Joohong Ahnn, Jeong Hoon Cho
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 390 Issue 1 Pg. 136-41 (Dec 04 2009) ISSN: 1090-2104 [Electronic] United States
• PMID: 19785996 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Caenorhabditis elegans Proteins
• Cation Transport Proteins
• natural resistance-associated macrophage protein 1
• pmr-1 protein, C elegans
• Manganese
• Edetic Acid
• Calcium-Transporting ATPases

Topics

• Animals
• Caenorhabditis elegans (genetics, metabolism, microbiology)
• Caenorhabditis elegans Proteins (genetics, metabolism)
• Calcium-Transporting ATPases (genetics, metabolism)
• Cation Transport Proteins (genetics, metabolism)
• Edetic Acid (pharmacology)
• Gene Knockdown Techniques
• Immunity, Innate
• Intestinal Mucosa (metabolism)
• Manganese (metabolism)
• Staphylococcus aureus