Bacterial magnetosome biomineralization - A novel platform to study molecular mechanisms of human CDF-related type-II diabetes

Natalie Zeytuni, René Uebe, Michal Maes, Geula Davidov, Michal Baram, Oliver Raschdorf, Assaf Friedler, Yifat Miller, Dirk Schüler, Raz Zarivach

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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.

Original languageAmerican English
Article numbere97154
JournalPLoS ONE
Volume9
Issue number5
DOIs
StatePublished - 12 May 2014

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