期刊
PLOS ONE
卷 9, 期 5, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0097154
关键词
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资金
- GIF (German-Israeli Foundation for Scientific Research and Development)
- European Cooperation in Science and Technology (COST action) [CM0902]
- Israeli Ministry of Science and Technology, the Deutsche Forschungsgemeinschaft [SCHU 1080/13-1]
- FP7 of the European Union [NMP4-SL-2010-245542-Bio2MaN4MRI]
- European Research Council under the European Community's Seventh Framework Programme (FP7)/ERC [203413]
- Minerva Center for bio-hybrid complex systems
- FP7-PEOPLE-2011-CIG [303741]
Cation diffusion facilitators (CDF) are part of a highly conserved protein family that maintains cellular divalent cation homeostasis in all organisms. CDFs were found to be involved in numerous human health conditions, such as Type-II diabetes and neurodegenerative diseases. In this work, we established the magnetite biomineralizing alphaproteobacterium Magnetospirillum gryphiswaldense as an effective model system to study CDF-related Type-II diabetes. Here, we introduced two ZnT-8 Type-II diabetes-related mutations into the M. gryphiswaldense MamM protein, a magnetosome-associated CDF transporter essential for magnetite biomineralization within magnetosome vesicles. The mutations' effects on magnetite biomineralization and iron transport within magnetosome vesicles were tested in vivo. Additionally, by combining several in vitro and in silico methodologies we provide new mechanistic insights for ZnT-8 polymorphism at position 325, located at a crucial dimerization site important for CDF regulation and activation. Overall, by following differentiated, easily measurable, magnetism-related phenotypes we can utilize magnetotactic bacteria for future research of CDF-related human diseases.
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