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

Luís António Menezes Carreira, Dobromir Szadkowski, Stefano Lometto, Georg. K. A. Hochberg and Lotte Søgaard-Andersen ()
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Luís António Menezes Carreira: Max Planck Institute for Terrestrial Microbiology
Dobromir Szadkowski: Max Planck Institute for Terrestrial Microbiology
Stefano Lometto: Evolutionary Biochemistry Group, Max Planck Institute for Terrestrial Microbiology
Georg. K. A. Hochberg: Evolutionary Biochemistry Group, Max Planck Institute for Terrestrial Microbiology
Lotte Søgaard-Andersen: Max Planck Institute for Terrestrial Microbiology

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-39773-y

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