Lotte Sogaard-Andersen
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Bacterial development and differentiation
Positive regulation of cell division in bacteria
In all cells, accurate positioning of the cell division site is essential for generating appropriately-sized daughter cells with a correct chromosome number. In bacteria, cell division generally occurs at mid-cell and initiates with assembly of the tubulin homologue FtsZ into a circumferential ring-like structure, the Z-ring, at the incipient division site. Subsequently, FtsZ recruits the remaining components of the cell division machinery needed to carry out cytokinesis. Thus, the position of Z-ring formation dictates the cell division site. Accordingly, all known systems that regulate positioning of the division site in bacteria control Z-ring positioning. In other bacteria, regulators of Z-ring formation act negatively to inhibit Z-ring formation at the cell poles and over the nucleoid, leaving only mid-cell free for Z-ring formation.
M. xanthus cells are rod-shaped and divide by binary fission. Serendipitously, we were recently able to show that the PomZ protein, which is a member of the ParA/Soj subfamily of P-loop ATPases, regulates positioning of the cell division site in M. xanthus. In particular, we were able to show that lack of PomZ results in a severe reduction in Z-ring formation, and abnormal positioning of the few Z-rings formed. PomZ localization changes with cell cycle progression and culminates in the localization to the incipient division site at mid-cell before FtsZ. The recruitment of FtsZ to mid-cell by PomZ is likely direct because the two proteins interact in vitro. Based on these observations we have proposed that PomZ is a novel spatial regulator of cell division that provides positional information for Z-ring formation in that way positively regulating positioning of the cell division site. In addition, our data suggest that PomZ stabilizes the Z-ring. In principle, specification of the cell division site can depend on positively acting systems that precisely define the site of cell division, on negatively acting systems that inhibit cell division everywhere in a cell except at the incipient division site, or a combination of both. In eukaryotic cells a combination of positive and negative signals specifies the site of cell division whereas in bacteria selection of the site of cell division has been thought to rely on negatively acting systems only. The finding that PomZ positively regulates cell division site positioning illustrates that bacteria also employ positively acting systems to specify the site of cell division. We are currently focusing on understanding how PomZ localizes in distinct patterns during the cell cycle and in particular how PomZ is directed to mid-cell and if that involves signals from the segregating chromosomes as is the case in eukaryotic cells.
Model of PomZ-dependent recruitment of FtsZ to mid-cell