The divisome at 25: the road ahead

Abstract

The identification of the FtsZ ring by Bi and Lutkenhaus in 1991 was a defining moment for the field of bacterial cell division. Not only did the presence of the FtsZ ring provide fodder for the next 25 years of research, the application of a then cutting-edge approach-immunogold labeling of bacterial cells-inspired other investigators to apply similarly state-of-the-art technologies in their own work. These efforts have led to important advances in our understanding of the factors underlying assembly and maintenance of the division machinery. At the same time, significant questions about the mechanisms coordinating division with cell growth, DNA replication, and chromosome segregation remain. This review addresses the most prominent of these questions, setting the stage for the next 25 years.

Figure 1.

A. Bacterial cell division time-line of discovery. B. Division cycle progression time-line. Note that timing of division-related events are based on work in MC4100 cells cultured in minimal glucose medium [37,102]. Initiation time was calculated based on an 80 minute mass doubling period using the CCSim program available at https://sils.fnwi.uva.nl/bcb/cellcycle/ [103]

Figure 2.

FtsZ polymers serve as GTP-dependent treadmills for the cell wall synthesis machinery in E. coli and B. subtilis. The peptidoglycan synthesis machinery (green) is tethered to short FtsZ filaments (yellow). FtsZ-dependent GTP hydrolysis stimulates treadmilling in which GTP bound monomers are added to the putative (+) end of the filament and GDP bound monomers are released from the (−) end. Treadmilling leads to the processive insertion of cell wall material at the septum. In E. coli, the positive regulators of division, ZapA (green) and ZapB (red) help organize FtsZ polymers within the divisome. ZapB helps coordinate division with DNA replication via interactions with the terminus binding protein MatP (gray).

Figure 3.

The E. coli divisome consists of two sets of factors: the early proteins (FtsZ, FtsA, ZipA, and ZapB in this figure), which constitute the proctoring, and the late proteins, whose recruitment is subsequent to and dependent upon the early proteins. FtsN bridges the early and late proteins, interacting with FtsA to stabilize the FtsQLB complex in the periplasm, and with FtsI/PBP3 and FtsW to stimulate cell wall synthesis (the latter interaction is not shown). Green starbursts indicate pre-activation state of FtsA, FtsN, FtsW and FtsI/PBP3 while green and red starburst indicates activated state. Additionally, FtsEX mediated ATP hydrolysis stimulates amidase activity (AmiA in this figure), thereby coordinating cell wall synthesis with hydrolysis to facilitate daughter cell separation. The model is not meant to reflect actual interaction stoichiometries, because they have yet to be determined. In addition, it is not yet clear if the amidases remain in complex with EnvC as drawn or if this interaction is also regulated. See text for details.