Spatial control of the GTPase MgIA by localized RomR-RomX GEF and MgIB GAP activities enables Myxococcus xanthus motility

The rod-shaped Myxococcus xanthus cells move with defined front-rear polarity using polarized motility systems. A polarity module consisting of the small GTPase MgIA, its cognate GTPase activating protein (GAP) MgIB and RomR establishes this polarity. Agl-Glt gliding motility complexes assemble and disassemble at the leading and lagging pole, respectively. These processes are stimulated by MgIA-GTP at the leading and MgIB at the lagging pole. Here, we identify RomX as an integral component of the polarity module. RomX and RomR form a complex that has MgIA guanine nucleotide exchange factor (GEF) activity and also binds MgIA-GTP. In vivo RomR recruits RomX to the leading pole forming the RomR-RomX complex that stimulates MgIA-GTP formation and binding, resulting in a high local concentration of MgIA-GTP. The spatially separated and opposing activities of the RomR-RomX GEF at the leading and the MgIB GAP at the lagging cell pole establish front-rear polarity by allowing the spatially separated assembly and disassembly of Agl-Glt motility complexes. Our findings uncover a regulatory system for bacterial cell polarity that incorporates a nucleotide exchange factor as well as an NTPase activating protein for regulation of a nucleotide-dependent molecular switch and demonstrate a spatial organization that is conserved in eukaryotes.