Splitsville: structural and functional insights into the dynamic bacterial Z ring

Key Points All cells must divide to proliferate, and most bacteria divide by splitting themselves into two during cytokinesis. Many bacteria divide by splitting into approximately equal halves in a process called binary fission. Cytokinesis in bacteria is achieved by the divisome, a dedicated protein machine that is located at the site of cell division. Recent advances in ultrastructural imaging, biochemistry and genetics of Escherichia coli and other model bacterial species have helped to refine models of divisome function and regulation. FtsZ, the bacterial homologue of tubulin, is the principal driver of bacterial cytokinesis. In vitro , FtsZ assembles into single protofilaments in the presence of GTP. In vivo , these protofilaments loosely assemble to encircle the cell at the site of division — called the Z ring — and are positioned there by species-specific spatial positioning proteins. As FtsZ is a soluble protein, FtsZ protofilaments must be tethered to the inner surface of the cytoplasmic membrane by additional proteins, including FtsA and ZipA in E. coli . This complex of FtsZ and membrane tethers is called the proto-ring and has highly dynamic behaviour. Although they do not form microtubules, FtsZ protofilaments self-associate to form bundles, either through interactions with other FtsZ subunits or with several FtsZ-binding proteins that enhance bundling, including ZipA and Zap proteins. These lateral interactions between FtsZ protofilaments may be important for the ability of FtsZ to divide a cell. FtsA, a bacterial homologue of actin, is a key connector between the Z ring and other proteins of the divisome, all of which span the membrane and some of which bind to the peptidoglycan layer. Once the divisome is completely assembled, it coordinates the inward constriction of the Z ring and cytoplasmic membrane with the synthesis of the cell division septum, which is composed of peptidoglycan. FtsA is a key player in this coordination, which probably involves feedback signalling between the peptidoglycan-binding divisome proteins and the Z ring. Biochemical characterization of FtsA remains a major challenge. In addition to signalling in the divisome during the process of cytokinesis, the divisome is regulated by mechanical, metabolic and stress inputs. FtsZ is a major target for these regulators, but other divisome proteins are also targets. Understanding how divisome proteins are inhibited or stimulated will be valuable in the future design of div