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Molecular basis and design principles of a system for switchable front-rear polarity and directional migration

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Carreira,  Luis Antonio Menezes
Bacterial Adaption and Differentiation, Department of Ecophysiology, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

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Szadkowski,  Dobromir
Bacterial Adaption and Differentiation, Department of Ecophysiology, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

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Lometto,  Stefano
Max Planck Research Group Evolutionary Biochemistry, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

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Hochberg,  Georg K. A.       
Max Planck Research Group Evolutionary Biochemistry, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

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Søgaard-Andersen,  Lotte       
Bacterial Adaption and Differentiation, Department of Ecophysiology, Max Planck Institute for Terrestrial Microbiology, Max Planck Society;

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Citation

Carreira, L. A. M., Szadkowski, D., Lometto, S., Hochberg, G. K. A., & Søgaard-Andersen, L. (2022). Molecular basis and design principles of a system for switchable front-rear polarity and directional migration. bioRxiv: the preprint server for biology, 2022.12.09.519731.


Cite as: https://hdl.handle.net/21.11116/0000-000B-F27D-8
Abstract
During cell migration, front-rear polarity is spatiotemporally regulated; however, the underlying design of regulatory interactions vary. In rod-shaped Myxococcus xanthus cells, a spatial toggle switch dynamically regulates front-rear polarity. The polarity module establishes front-rear polarity by guaranteeing front pole-localization of the small GTPase MglA. Conversely, the Frz chemosensory system, by acting on the polarity module, causes polarity inversions. MglA localization depends on the RomR/RomX GEF and MglB/RomY GAP complexes that localize asymmetrically to the poles by unknown mechanisms. Here, we show that RomR and the MglB and MglC roadblock domain proteins generate a positive feedback by forming a RomR/MglC/MglB complex, thereby establishing the rear pole with high GAP activity that is non-permissive to MglA. MglA at the front engages in negative feedback that inhibits the RomR/MglC/MglB positive feedback allosterically, thus ensuring low GAP activity at this pole. These findings unravel the design principles of a system for switchable front-rear polarity.Competing Interest StatementThe authors have declared no competing interest.