Functional assessment of Nramp-like metal transporters and manganese in Caenorhabditis elegans |
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Authors: | Jaya Bandyopadhyay Hyun-Ok Song Byung-Jae Park Gunasekaran Singaravelu Joohong Ahnn |
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Institution: | a Department of Biotechnology, West Bengal University of Technology, Kolkata 700-064, India b Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea c Department of Life Science, Hallym University, Chuncheon 200-702, Republic of Korea d Department of Life Science, Hanyang University, Seoul 133-791, Republic of Korea e Division of Biology Education, College of Education, Chosun University, Gwangju 501-759, Republic of Korea |
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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. |
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Keywords: | Caenorhabditis elegans Nramp homologs Mn feeding Pathogen Caenorhabditis elegans intestine Innate immunity pmr-1 |
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