Similarly to eukaryotic cells bacterial cells are also spatially highly organized and display polarity with individual chromosomal loci, mRNA’s, proteins, and lipids localizing to specific subcellular regions. Moreover, several proteins localize dynamically and change localization pattern over time. For most dynamically localized proteins, the localization pattern changes in a cell cycle dependent manner. An exception to this general rule are motility proteins in Myxococcus xanthus that localize dynamically to the cell poles in a cell cycle-independent manner, i.e. during a cellular reversal motility proteins localizing to the lagging cell pole switch to the new lagging cell pole and proteins and the leading cell pole switch to the new leading cell pole. The goal of this project is to identify and characterize the components of the regulatory system that underlies the dynamic polarity of motility proteins in M. xanthus. On the basis of this system, we long term aim to define a minimal module for regulation of dynamic cell polarity in bacteria and to establish this system in other microorganisms as well as in synthetic cells.
The regulatory system that controls polarity in M. xanthus is built around the MglA and MglB proteins, which define the leading/lagging pole polarity axis. MglA is a small Ras-like GTPase that functions as a nucleotide-dependent molecular switch to regulate motility in M. xanthus. The MglB protein functions as a GTPase activating protein (GAP) and converts active MglA/GTP to the inactive MglA/GDP. Between reversals MglA/GTP localizes to the leading cell pole while MglB localizes to the lagging cell pole. The two proteins bind to the two poles in a mutually exclusive manner and define the leading/lagging pole polarity axis. Our data suggest that MglA/GTP between reversals sets up the correct polarity of dynamically motility proteins. In response to signaling activity of the Frz chemosensory system MglA/GTP is released from the leading pole and relocates to the old lagging cell pole and as a consequence, MglB relocates to the old leading pole. In total, this results in an inversion of the leading/lagging pole polarity axis and the relocation of dynamic motility proteins.