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bioRxiv · 10.1101/2022.12.09.519731

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

Carreira, L. A. M.·Szadkowski, D.·Lometto, S.·Hochberg, G. K. A.·Sogaard-Andersen, L.
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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.

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Carreira, L. A. M., Szadkowski, D., Lometto, S., Hochberg, G. K. A., Sogaard-Andersen, L.. 2022-12-09. Molecular basis and design principles of a system for switchable front-rear polarity and directional migration. https://doi.org/10.1101/2022.12.09.519731

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