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Bacterial cell division: assembly, maintenance and disassembly of the Z ring

Key Points

  • The first recognizable event in bacterial cell division is the assembly of FtsZ into a ring-like structure at mid-cell. This Z ring serves as a scaffold for the assembly of the division machinery and contracts throughout division, guiding the synthesis of the nascent septum.

  • FtsZ is the ancestral homologue of tubulin and assembles cooperatively, in a GTP-dependent manner, into longitudinal protofilaments similar to those of αβ-tubulin. Although the polymerization of FtsZ in vitro has been studied extensively, little is known about the architecture of the polymers that make up the Z ring in vivo.

  • Importantly, the concentration of FtsZ in vivo is greatly in excess of the critical concentration for assembly. Despite this, the intracellular concentration of FtsZ does not vary greatly during the cell cycle. The initiation of cell division is instead regulated both spatially and temporally at the level of Z ring assembly, by an array of accessory proteins that can modulate the polymerization of FtsZ.

  • FtsZ is a cytoplasmic protein, but it must be tethered to the inner face of the cytoplasmic membrane to form the Z ring. This is achieved primarily by the action of FtsA, which is widely conserved and contains an amphipathic membrane-targeting sequence. Where present, ZipA, an integral membrane protein, can also allow Z ring assembly and, along with ZapA, also contributes to the stability of the Z ring.

  • Other, early-assembling regulators, such as ZapB and SepF, potentially play a part in organizing the ultrastructure of the Z ring and, although it is not normally essential, SepF seems to contribute to this process and might also be able to act as a membrane tether.

  • The Z ring is not a static structure. The polymers that constitute the Z ring are in a state of flux, with subunits rapidly exchanging between the polymer and the cytoplasmic pool. This turnover is stimulated by GTP hydrolysis and is regulated by the antagonistic behaviour of many non-essential proteins, including ZapA, extra Z rings A (EzrA) and ClpX.

  • Several regulatory proteins also render the Z ring responsive to variations in the cell cycle by taking advantage of the accessibility of subunits that is afforded by the dynamic nature of the Z ring. UgtP delays cell division by destabilizing the Z ring, and the induction of SulA during the SOS response prevents new Z ring assembly and disassembles existing Z rings. In addition, during sporulation, mother cell inhibitor of FtsZ (MciZ) prevents inappropriate cell division once the process has been initiated.

Abstract

Bacterial cell division is orchestrated by a tubulin homologue, FtsZ, which polymerizes to form a ring-like structure that is both a scaffold for the assembly of the bacterial cytokinetic machinery and, at least in part, a source of the energy for constriction. FtsZ assembly is tightly regulated, and a diverse repertoire of accessory proteins contributes to the formation of a functional division machine that is responsive to cell cycle status and environmental stress. In this Review, we describe the interaction of these proteins with FtsZ and discuss recent advances in our understanding of Z ring assembly.

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Figure 1: Cell division in rod-shaped bacteria.
Figure 2: FtsZ polymerization.
Figure 3: Regulation of FtsZ assembly by accessory proteins.

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Acknowledgements

We apologise to colleagues whose work has not been cited in full owing to space constraints. We thank members of the Centre for Bacterial Cell Biology for stimulating discussions and L. Hamoen for helpful comments on the manuscript. Work on cell division in the Errington laboratory is supported by a grant from the Biotechnology and Biological Sciences Research Council (BBSRC). D.W.A is supported by a BBSRC CASE studentship with Prolysis.

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DATABASES

Entrez Genome Project

Bacillus subtilis

Caulobacter crescentus

Corynebacterium glutamicum

Escherichia coli

Mycoplasma mobile

Staphylococcus aureus

Streptococcus pneumoniae

Synechococcus elongatus

Thermotoga maritima

Ureaplasma urealyticum

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Glossary

Cooperative assembly

Assembly that is characterized by the increased affinity of individual subunits for the growing polymer rather than for each other. Polymerization displays a sigmoidal relationship with concentration and has a defined critical concentration, below which no significant assembly occurs.

Cryo-electron microscopy tomography

A technique that allows the visualization of biological molecules in a near-native state. Unfixed samples are flash frozen, held at cryogenic temperature and visualized by transmission electron microscopy. Tomography uses a series of tilted images from which a three-dimensional image of the sample can be deduced.

Fluorescence recovery after photobleaching

A live-cell imaging technique used to monitor the intracellular dynamics of fluorescently tagged molecules. A target region is irreversibly photobleached by a laser and then monitored for recovery of fluorescence. Dynamics are expressed in terms of the half-time for recovery (the time taken to reach half of the original fluorescence intensity).

Bitopic protein

A protein that contains a single transmembrane segment between the cytoplasmic and extracytoplasmic domains.

ftsZ84

A mutation that results in the substitution of glycine to serine at position 105 in Escherichia coli FtsZ. This substitution reduces both the GTP binding and the GTPase activity of FtsZ in vitro and renders the protein temperature sensitive in vivo.

Synthetic lethal

Lethality due to a combination of two non-lethal mutations.

90°-angle light scattering

A real-time assay that measures the amount of light that is scattered by FtsZ polymers. The increase in signal is proportional to the extent of Z ring assembly, and the method can also be used to follow disassembly.

Lipoteichoic acid

A class of teichoic acids that is anchored in the cell membrane. Teichoic acids are anionic polymers that are ubiquitous in the cell walls of Gram-positive bacteria.

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Adams, D., Errington, J. Bacterial cell division: assembly, maintenance and disassembly of the Z ring. Nat Rev Microbiol 7, 642–653 (2009). https://doi.org/10.1038/nrmicro2198

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