Spatial control of the GTPase MglA by localized RomR–RomX GEF and MglB 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 MglA, its cognate GTPase activating protein (GAP) MglB 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 MglA-GTP at the leading and MglB at the lagging pole. Here, we identify RomX as an integral component of the polarity module. RomX and RomR form a complex that has MglA guanine nucleotide exchange factor (GEF) activity and also binds MglA-GTP. In vivo RomR recruits RomX to the leading pole forming the RomR–RomX complex that stimulates MglA-GTP formation and binding, resulting in a high local concentration of MglA-GTP. The spatially separated and opposing activities of the RomR–RomX GEF at the leading and the MglB 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. The GTPase MglA, its cognate GTPase activating protein (GAP) MglB and RomR are known to regulate gliding motility in Myxococcus xanthus . There are no known cognate guanine nucleotide exchange factors (GEFs) for MglA. Here, RomX is identified as a binding partner of RomR, and their complex serves as an MglA GEF.