Molecular basis and design principles of switchable front-rear polarity and directional migration in Myxococcus xanthus

Cell polarity is key to many processes in bacteria. By focusing on the roadblock domain protein MglC, the authors elucidate the mechanistic basis and design principles of a system that spatiotemporally regulates switchable front-rear polarity and directional migration. During cell migration, front-rear polarity is spatiotemporally regulated; however, the underlying design of regulatory interactions varies. 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 breaks 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.

Automated summary

Cell polarity plays a key role in bacterial processes. The authors focus on the protein MglC to understand the mechanism and design principles of a system that regulates switchable front-rear polarity and directional migration. They find that a feedback loop involving RomR, MglC, and MglB establishes front-rear polarity and controls the activity of the small GTPase MglA.