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

• Published in: Nature communications Vol. 14; no. 1; p. 4056
• Main Authors: Carreira, Luís António Menezes, Szadkowski, Dobromir, Lometto, Stefano, Hochberg, Georg K A, Søgaard-Andersen, Lotte
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 08.07.2023; Nature Publishing Group UK; Nature Portfolio
• Subjects: Cell migration; Chemoreception; Design; Feedback; Inversions; Localization; Modules; Myxococcus xanthus; Negative feedback; Polarity; Positive feedback; Principles; Proteins
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-39773-y

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.